داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ دوره 70
ﺷﻤﺎره 2
اردﻳﺒﻬﺸﺖ 1391
ﺻﺎﺣﺐ اﻣﺘﻴﺎز :داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ﻣﺪﻳﺮ ﻣﺴﺆول :دﻛﺘﺮ ﺳﻴﺪ ﺣﺴﻦ اﻣﺎﻣﻲرﺿﻮي ﺳﺮدﺑﻴﺮ :دﻛﺘﺮ ﻧﺎدره ﺑﻬﺘﺎش ﻣﺪﻳﺮ اﺟﺮاﻳﻲ :دﻛﺘﺮ ﻣﺤﻤﺪ ﻋﻠﻲ ﻧﻮﻳﺎن اﺷﺮف ﺷﻮراي دﺑﻴﺮان
دﻛﺘﺮ ﺷﺎﻫﻴﻦ آﺧﻮﻧﺪزاده ،دﻛﺘﺮ ﺻﺪﻳﻘﻪ ﺑﺮﻧﺎ ،دﻛﺘﺮ ﺟﻤﺸﻴﺪ ﺣﺎﺟﺘﻲ ،دﻛﺘﺮ ﻋﻠﻴﺮﺿﺎ ﺧﻮﺷﻨﻮﻳﺴﺎن ،دﻛﺘﺮ ﻧﻴﻤﺎ رﺿﺎﻳﻲ ،دﻛﺘﺮ ﻧﮕﺎر ﺳﺠﺎدﻳﺎن، دﻛﺘﺮ ﻋﻠﻲ ﻋﺮبﺧﺮدﻣﻨﺪ ،دﻛﺘﺮ ﻧﻌﻤﺖاﷲ ﻋﻄﺎﻳﻲ ،دﻛﺘﺮ راﻣﺶ ﻋﻤﺮاﻧﻲﭘﻮر ،دﻛﺘﺮ ﻣﺤﻤﻮد ﻗﺎﺿﻲ ﺧﻮاﻧﺴﺎري ،دﻛﺘﺮ ﺳﻴﺪﺟﻮاد ﻗﺎﺿﻲ ﻣﻴﺮ ﺳﻌﻴﺪ، دﻛﺘﺮ ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ ،دﻛﺘﺮ ﺳﻴﻨﺎ ﻣﺮادﻣﻨﺪ ،دﻛﺘﺮ زﻳﻨﺖ ﻧﺎدﻳﺎﺣﺘﻤﻲ ،دﻛﺘﺮ ﻣﺤﻤﺪ ﻋﻠﻲ ﻧﻮﻳﺎن اﺷﺮف ﻫﻴﺄت ﺗﺤﺮﻳﺮﻳﻪ
دﻛﺘﺮ ﻧﺎﺻﺮ اﺑﺮاﻫﻴﻤﻲ درﻳﺎﻧﻲ ،دﻛﺘﺮ ﻣﺤﻤﻮد اﻛﺒﺮﻳﺎن ،دﻛﺘﺮ ﻓﺮﻧﺎز آﻣﻮزﮔﺎر ﻫﺎﺷﻤﻲ ،دﻛﺘﺮ ﺑﺎﺑﻚ ﺑﻬﺎر ،دﻛﺘﺮ ﭘﺮوﻳﻦ ﭘﺎﺳﺎﻻر ،دﻛﺘﺮ ﭘﺮﻳﭽﻬﺮ ﭘﺎﺳﺒﺨﺶ، دﻛﺘﺮ زاﻫﺪ ﺣﺴﻴﻦ ﺧﺎن ،دﻛﺘﺮ زﻫﺮا ﺣﻼﺟﻲ ،دﻛﺘﺮ ﻓﺎﻃﻤﻪ داوري ﺗﻨﻬﺎ ،دﻛﺘﺮ ﻣﻬﺮﻧﺎز رﺳﻮﻟﻲﻧﮋاد ،دﻛﺘﺮ ﻣﺴﻌﻮد ﺳﺘﻮده ،دﻛﺘﺮ ﻋﻠﻴﺮﺿﺎ ﺷﻌﺒﺎﻧﻲ، دﻛﺘﺮ اﺣﻤﺪرﺿﺎ ﻃﻼﺋﻲﭘﻮر ،دﻛﺘﺮ ﻣﺤﻤﺪرﺿﺎ ﻇﻔﺮﻗﻨﺪي ،دﻛﺘﺮ ﻣﺤﻤﺪ ﻛﺠﺒﺎفزاده ،دﻛﺘﺮ ﺳﻴﺪ ﻣﺤﻤﺪﺟﻮاد ﻣﺮﺗﻀﻮي ،دﻛﺘﺮ اﻋﻈﻢاﻟﺴﺎدات ﻣﻮﺳﻮي، دﻛﺘﺮ ﻣﺤﻤﺪﺟﻮاد ﻣﻴﻜﺎﺋﻴﻠﻲ ،دﻛﺘﺮ ﺑﻬﺮوز ﻧﺒﺌﻲ ،دﻛﺘﺮ ﻣﺮﺿﻴﻪ وﺣﻴﺪ دﺳﺘﺠﺮدي ،دﻛﺘﺮ ﻣﺤﻤﺪرﺿﺎ ﻫﺎدﻳﺎن ﻫﻴﺄت ﺗﺤﺮﻳﺮﻳﻪ ﺑﻴﻦ اﻟﻤﻠﻠﻲ
دﻛﺘﺮ ﻓﺮﻫﻨﺎك اﺳﺪي )ﺷﻴﻜﺎﮔﻮ( ،دﻛﺘﺮ ﺟﻮاد ﭘﺮوﻳﺰي )ﻓﻴﻼدﻟﻔﻴﺎ( ،دﻛﺘﺮ ﻣﺤﻤﺪرﺿﺎ ﻛﺸﺘﮕﺮ )ﻟﻨﺪن( ،دﻛﺘﺮ اﻓﺸﻴﻦ ﮔﻨﺠﻲ )اﺳﺘﺮاﺳﺒﻮرگ(، دﻛﺘﺮ ﺷﻬﻼ ﻣﺴﻌﻮد )ﻓﻠﻮرﻳﺪا( ،دﻛﺘﺮ ﭘﺮوﻳﺰ ﻫﻨﺠﻨﻲ )ﭘﻨﺴﻴﻠﻮاﻧﻴﺎ( وﻳﺮاﺳﺘﺎران
دﻛﺘﺮ ﻧﺎدره ﺑﻬﺘﺎش ،دﻛﺘﺮ ﻣﺤﻤﺪ ﻋﻠﻲ ﻧﻮﻳﺎن اﺷﺮف ،دﻛﺘﺮ وﺣﻴﺪ ﻧﻴﻜﻮﻳﻲ ،دﻛﺘﺮ ﺳﻴﺪ ﺑﻬﻨﺎم ﻫﺎﺷﻤﻲ ﻫﻤﻜﺎران دﻓﺘﺮ ﻣﺠﻠﻪ
ﺣﺴﻴﻦ ﭼﺎﻳﭽﻲ ،راﺣﻠﻪ رﻣﻀﺎﻧﻲ ،ﺳﺤﺮ ﺻﺪﻳﻖ ،ﻣﻌﺼﻮﻣﻪ ﻋﺴﮕﺮي ،آرزو ﻛﻤﻴﺰاﻧﻲ ﻧﺸﺎﻧﻲ :ﺗﻬﺮان ،ﺧﻴﺎﺑﺎن ﻗﺪس ،ﺧﻴﺎﺑﺎن ﭘﻮرﺳﻴﻨﺎ ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،ﺳﺎﺧﺘﻤﺎن آﻣﻮزش ،ﻃﺒﻘﻪ اول ،ﺷﻤﺎره ،202دﻓﺘﺮ ﻣﺠﻠﻪ آدرس اﻟﻜﺘﺮوﻧﻴﻚ http://tumj.tums.ac.ir :ﭘﺴﺖ اﻟﻜﺘﺮوﻧﻴﻚmedjournal@tums.ac.ir : ﺻﻨﺪوق ﭘﺴﺘﻲ ،14155/6447ﺗﻠﻔﻜﺲOnline submission: http://journals.tums.ac.ir/login ، 88962510 : ﺑﺮاﺳﺎس ﻣﺼﻮﺑﻪ ﻛﻤﻴﺴﻴﻮن ﻧﺸﺮﻳﺎت ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻛﺸﻮر ،ﺑﻪ ﻧﻮﻳﺴﻨﺪﮔﺎن ﻣﻘﺎﻻت اﻳﻦ ﻣﺠﻠﻪ اﻣﺘﻴﺎز ارﺗﻘﺎي ﻋﻠﻤﻲ ﭘﮋوﻫﺸﻲ ﺗﻌﻠﻖ ﻣﻲﮔﻴﺮد. ﺗﻴﺮاژ 1000 :ﻧﺴﺨﻪ
ﻟﻴﺘﻮﮔﺮاﻓﻲ ،ﭼﺎپ و ﺻﺤﺎﻓﻲ :ﺑﻬﺮﻧﮓ
)راﻳﮕﺎن(
ﻧﻤﺎﻳﻪ ﺷﺪه در:
SCOPUS, EMBASE, Cambridge Scientific Abstracts (CSA), CAB Abstracts (CABI), Chemical Abstract Service (CAS), DOAJ, Psych Info, ULRICH΄S, Index Copernicus, IMEMR, EMR Beta, SID, Magiran, Iran Medex
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان دوره 70
ﺷﻤﺎره 2
اردﻳﺒﻬﺸﺖ 1391
ﻓﻬﺮﺳﺖ ﺑﺮرﺳﻲ آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘﺲ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ از ﻣﻮش ﺳﻮري Inbredﻣﺒﺘﻼ ﺑﻪ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﻛﻠﻴﻮي69................................................. ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ ،ﺣﺴﻴﻦ ﺧﻮاﺳﺘﺎر ،ﺑﻬﺠﺖ ﺳﻴﻔﻲ ،ﻋﺎﻃﻔﻪ ﻧﺠﻔﻲ ،ﻓﺎﻃﻤﻪ دﻻوري
ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي و ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺗﺎﺛﻴﺮ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ ران ﻣﻮش ﺻﺤﺮاﻳﻲ78............................... ﻏﻔﻮر ﻣﻮﺳﻮي ،دارﻳﻮش ﻣﻬﺎﺟﺮي ،ﻋﻠﻲ رﺿﺎﻳﻲ ،ﻣﺤﻤﺪرﺿﺎ وﻟﻴﻠﻮ ،آرﻣﺎن ﻋﻠﻴﻤﺤﻤﺪي
ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﻪوﺳﻴﻠﻪ ﺗﻜﻨﻴﻚ RNAiدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﻛﺸﺖ داده ﺷﺪه روي دارﺑﺴﺖ ﺳﻪ ﺑﻌﺪي " DBMﻣﺎﺗﺮﻳﻜﺲ
اﺳﺘﺨﻮاﻧﻲ ﻣﻌﺪﻧﻲ زداﺷﺪه"86................................................................................................................................................................................. زﻫﺮااﻟﺴﺎدات ﻫﺎﺷﻤﻲ ،ﻣﻬﺪي ﻓﺮوزﻧﺪه ﻣﻘﺪم ،ﻣﺴﻌﻮد ﺳﻠﻴﻤﺎﻧﻲ ،ﻣﺮﻳﻢ ﺣﻔﻴﻈﻲ ،ﻧﺎﺻﺮ اﻣﻴﺮي زاده
ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي دﻫﺎﻧﻲ اﻓﺮاد آﻟﻮده ﺑﻪ HIVﻧﺴﺒﺖ ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﺗﺤﺖ ﺷﺮاﻳﻂ ﺑﺮون ﺗﻨﻲ در اﻳﺮان96..................................................... ﻓﺮزاد ﻛﺘﻴﺮاﺋﻲ ،ﻋﻠﻴﺮﺿﺎ ﺧﺴﺮوي ،وﺣﻴﺪ ﺧﻠﺞ ،ﻣﺤﺒﻮﺑﻪ ﺣﺎﺟﻲ ﻋﺒﺪاﻟﺒﺎﻗﻲ ،ﻋﻠﻲاﺻﻐﺮ ﺧﺎﻛﺴﺎر ،ﻣﻬﺮﻧﺎز رﺳﻮﻟﻲﻧﮋاد
ﺑﺮرﺳﻲ ﺗﻜﻨﻴﻚ ﺻﻔﺤﻪﮔﺬاري ﺑﻴﻮﻟﻮژﻳﻚ در ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ران104.............................................................................. ﺳﻌﻴﺪرﺿﺎ ﻣﻬﺮﭘﻮر ،ﻣﺤﻤﺪرﺿﺎ ﻃﻮاﻓﻲ ،رﺿﺎ ﺳﺮﺑﻲ ،ﻣﺤﻤﺪرﺿﺎ آﻗﺎﻣﻴﺮﺳﻠﻴﻢ
ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﺑﺮ ﭘﺎﺳﺦ ﺣﺎد آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن ﻣﺴﻦ 110.............................................................................................. دﻧﻴﺎ ﺻﻮرﺗﻲ ﺟﺎﺑﻠﻮ ،ﺳﻴﺪ رﺿﺎ ﻋﻄﺎرزاده ﺣﺴﻴﻨﻲ ،دﻻرام ﺻﻴﺎدﭘﻮر زﻧﺠﺎﻧﻲ ،اﻣﻴﻦ اﺣﻤﺪي
ﻣﻘﺎﻳﺴﻪ ﺗﺎﺛﻴﺮ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧﻞ ﻣﻔﺼﻠﻲ در درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ119............................................................................. ﺳﻴﺪ ﻣﺴﻌﻮد ﻫﺎﺷﻤﻲ ،ﻓﻴﺮوز ﻣﺪدي ،ﺳﻌﻴﺪ رﺿﻮي ،ﻣﻬﺸﻴﺪ ﻧﻴﻜﻮﺳﺮﺷﺖ ،ﻓﺮﺷﺎد ﺣﺴﻦ زاده ﻛﻴﺎﺑﻲ ،ﺳﻤﻴﻪ ﻧﺼﻴﺮي ﭘﻮر
ﺑﺮرﺳﻲ ﻓﺮاواﻧﻲ ﭘﻮﻟﻴﭗﻫﺎ و ﺑﺪﺧﻴﻤﻲﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل در زﻧﺎن ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان و اﻧﺪوﻣﺘﺮ در ﺳﺎل 1389-90
در ﺑﻴﻤﺎرﺳﺘﺎن ﻓﻴﺮوزﮔﺮ اﻛﺒﺮآﺑﺎدي و رﺳﻮل اﻛﺮم :ﮔﺰارش ﻛﻮﺗﺎه 126................................................................................................................................. ﺳﻴﻤﺎ ﺟﻌﻔﺮي ،ﺳﻴﺎﻣﻚ ﺧﺎﻟﻘﻲ ،ﻋﻠﻲ ﺑﺎﺳﻲ ،ﻃﻴﺐ رﻣﻴﻢ
ﺧﺼﻮﺻﻴﺎت ﺑﺎﻟﻴﻨﻲ ،آزﻣﺎﻳﺸﮕﺎﻫﻲ و اﭘﻴﺪﻣﻴﻮﻟﻮژﻳﻚ ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺑﺮوﺳﻠﻮز در اﺳﺘﺎن ﻫﻤﺪان:
ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﮔﺬﺷﺘﻪﻧﮕﺮ روي 230ﺑﻴﻤﺎر :ﮔﺰارش ﻛﻮﺗﺎه 130............................................................................................................................................. ﭘﻴﻤﺎن ﻋﻴﻨﻲ ،ﻓﺮزاﻧﻪ اﺛﻨﻲ ﻋﺸﺮي ،اﺣﻤﺪ رﺿﺎ ﻣﺒﻴﻦ ،ﻣﻬﺪي ﺣﺴﻦ زاده
درﻣﺎن ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ واﺑﺴﺘﻪ ﺑﻪ اﻳﺪز :ﮔﺰارش ﻣﻮردي 136............................................................................................................................................. زﻫﺮا ﻋﺒﺪي ،ﻧﺪا ﻋﻠﻴﺠﺎﻧﻲ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
راﻫﻨﻤﺎي ﻧﻮﻳﺴﻨﺪﮔﺎن -1اﺻﻮل ﻛﻠﻲ -1 :آﻳﻴﻦ ﻧﮕﺎرش زﺑﺎن ﻓﺎرﺳﻲ رﻋﺎﻳﺖ ﺷﺪه و از ﺑﻪﻛﺎر ﺑـﺮدن ﻛﻠﻤـﺎت
ﺑﺎﺷﺪ و ﻋﻨﻮان ﺟﺪول ،ﺑﺎﻻي آن و در ﻧﻤﻮدار ،زﻳﺮ آن ﻗﺮار ﮔﻴﺮد )ﺑﺎ ذﻛـﺮ ﺷـﻤﺎره( .ﺑـﺎ
ﺧــﺎرﺟﻲ ﻛــﻪ ﻣﻌــﺎدل رﺳــﺎ در ﻓﺎرﺳــﻲ دارﻧــﺪ ،ﺧــﻮدداري ﺷــﻮد -2 .ﻣﻘــﺎﻻت ﺑــﻪ
ﺗﻮﺟﻪ ﺑﻪ ﻣﺤﺪودﻳﺖ ﺻﻔﺤﺎت ﻣﺠﻠﻪ ،ﺑﺪﻳﻬﻲ اﺳﺖ از ﺗﻜﺮار اراﻳﻪ ﻣﻄـﺎﻟﺒﻲ ﻛـﻪ در ﻣـﺘﻦ
آدرس اﻟﻜﺘﺮوﻧﻴﻚ ﻣﺠﻠﻪ " "http://journals.tums.ac.ir/login.aspxارﺳـﺎل ﮔـﺮدد
آورده ﺷﺪهاﻧﺪ در ﺟﺪاول و ﺑﺎﻟﻌﻜﺲ ﺑﺎﻳﺪ اﺟﺘﻨﺎب ﻧﻤﻮد ،ﺟـﺪاول و ﻧﻤﻮدارﻫـﺎ ﻓﺎرﺳـﻲ
) Microsoft word 2003ﻳـﺎ ﺑﺎﻻﺗﺮ( -3 .ﻣﻘﺎﻟﻪ ﺑﻪﻃﻮر ﻫﻢزﻣـﺎن ﺑـﺮاي ﺳـﺎﻳﺮ ﻣﺠـﻼت
ﺑﺎﺷﻨﺪ .ﻋﻜﺲﻫﺎ ،ﻧﻤﻮدارﻫﺎ و ﺟﺪاول ﻣﺮﺑﻮط ﺑﻪ ﻣﻘﺎﻟﻪ ﺑﻪﻫﻤﺮاه ﺗﻮﺿﻴﺤﺎت آنﻫﺎ ﺑﺎﻳﺴﺘﻲ
ارﺳﺎل ﻧﮕﺮدد و در ﺳﺎﻳﺮ ﻣﺠﻼت )ﺣﺘﻲ ﺑﻪ زﺑﺎن اﻧﮕﻠﻴﺴﻲ و ﻏﻴﺮه( ﺑﻪ ﭼﺎپ ﻧﺮﺳﻴﺪه
ﺟﺪاﮔﺎﻧﻪ و در دﻧﺒﺎﻟﻪ ﻣﺘﻦ اﺻﻠﻲ ﻣﻘﺎﻟﻪ آورده و ﺷﻤﺎرهﮔـﺬاري ﮔـﺮدد .ﻛﻴﻔﻴـﺖ ﺗـﺼﺎوﻳﺮ
ﺑﺎﺷﺪ -4 .ﻣﻘﺎﻻت ﭘﺬﻳﺮﻓﺘﻪ ﺷﺪه ﺷﺎﻣﻞ ﻣﻘـﺎﻻت ﺗﺤﻘﻴﻘـﻲ ،ﻣـﺮوري ،ﮔـﺰارش ﻛﻮﺗـﺎه و
ارﺳﺎﻟﻲ ﻣﻄﻠﻮب ﺑﺎﺷﺪ.
ﮔﺰارش ﻣﻮردي ﻣﻲﺑﺎﺷﺪ -5 .در اﻧﺠﺎم ﭘـﮋوﻫﺶ ،اﺻـﻮل ﺑﻴﺎﻧﻴـﻪ ﻫﻠـﺴﻴﻨﻜﻲ ) (2008و
ﺑﺤﺚ -1 :آﺛﺎر و اﻫﻤﻴﺖ ﻳﺎﻓﺘﻪﻫﺎي ﺑﻪدﺳﺖ آﻣﺪه و ﻣﺤﺪودﻳﺖ آنﻫﺎ -2 .ذﻛﺮ ﻧﺘـﺎﻳﺞ
ﺿﻮاﺑﻂ اﺧﻼق ﭘﺰﺷﻜﻲ رﻋﺎﻳﺖ ﮔﺮدد.
ﺗﺤﻘﻴﻖ ﻣﺸﺎﺑﻪ دﻳﮕﺮان و ذﻛﺮ ﻣﻐﺎﻳﺮات و ﻣﻮارد ﻧﻘﺾﻛﻨﻨﺪه -3 .ﺗﻮﺿﻴﺢ ﻋﻠـﺖ ﺗﻔـﺎوت
-2ﻧﺤﻮه ﺗﻨﻈﻴﻢ ﻣﻘﺎﻻت ﺗﺤﻘﻴﻘﻲ -1 :ﺻﻔﺤﻪ اول )ﻋﻨﻮان( ﺷﺎﻣﻞ ﻋﻨﻮان ﻣﻘﺎﻟـﻪ ،ﻧـﺎم و
ﺑﻴﻦ ﻧﺘﺎﻳﺞ اﻳﻦ ﺗﺤﻘﻴﻖ ﺑﺎ ﻣﻘﺎﻻت ﻗﺒﻠـﻲ -4 .ﺗﻮﺿـﻴﺢ ﻣـﻮارد ﻛـﺎرﺑﺮد ﻋﻤﻠـﻲ و ﻗﺎﺑﻠﻴـﺖ
ﻧﺎمﺧﺎﻧﻮادﮔﻲ ﻧﻮﻳﺴﻨﺪﮔﺎن ،درﺟﻪ ﻋﻠﻤـﻲ و آدرس دﻗﻴـﻖ ﻛﻠﻴـﻪ ﻧﻮﻳـﺴﻨﺪﮔﺎن )از ﺟﻤﻠـﻪ
ﺗﻌﻤﻴﻢﭘﺬﻳﺮي ﻧﺘﺎﻳﺞ -5 .راﻫﻨﻤﺎﻳﻲ ﺑﺮاي اداﻣﻪ ﺗﺤﻘﻴﻖ ﺧﻮد ﻳﺎ دﻳﮕﺮان ،در ﻣﺠﻤﻮع اراﻳـﻪ
ﻛﺪﭘﺴﺘﻲ ،ﺗﻠﻔﻦ ،دورﻧﮕﺎر و ﭘﺴﺖ اﻟﻜﺘﺮوﻧﻴﻚ( ﻣﺤﻞ اﻧﺠﺎم ﭘـﮋوﻫﺶ ،ﻣـﺴﺌﻮل ﻣﻘﺎﻟـﻪ و ﺗﺎرﻳﺦ ارﺳﺎل ﻣﻘﺎﻟﻪ ﺑﺎﺷﺪ -2 .ﺻﻔﺤﻪ دوم و ﺳﻮم ﺷﺎﻣﻞ ﺧﻼﺻﺔ ﻓﺎرﺳـﻲ و اﻧﮕﻠﻴـﺴﻲ و ﻛﻠﻤﺎت ﻛﻠﻴﺪي ﻓﺎرﺳﻲ و اﻧﮕﻠﻴﺴﻲ ﺑﺎﺷﺪ. ﭼﻜﻴﺪه ﻓﺎرﺳﻲ 240-250 :ﻛﻠﻤﻪ و در ﭼﻬﺎر ﭘﺎراﮔﺮاف ﺑﺎ ﻋﻨﺎوﻳﻦ زﻣﻴﻨـﻪ و ﻫـﺪف، روشﺑﺮرﺳﻲ ،ﻳﺎﻓﺘﻪﻫﺎ ،ﻧﺘﻴﺠﻪﮔﻴﺮي و ﻛﻠﻤـﺎت ﻛﻠﻴـﺪي )ﺣـﺪاﻗﻞ 3و ﺣـﺪاﻛﺜﺮ 7واژه( ﺗﻨﻈﻴﻢ ﺷﻮد .ﺗﻮﺻﻴﻪ ﻣﻲﺷﻮد ﻧﺴﺒﺖ 1-2-2-1در ﺗﻬﻴﻪ ﭼﻜﻴﺪه ﺑـﺎ ﭼﻬـﺎر ﻋﻨـﻮان ﻓـﻮق ﻟﺤﺎظ ﺷﻮد .ﭼﻜﻴﺪه اﻧﮕﻠﻴﺴﻲ ﺑﺎﻳﺪ ﻣﻨﻄﺒﻖ ﺑﺎ ﭼﻜﻴـﺪه ﻓﺎرﺳـﻲ ﺑﺎﺷـﺪ و در ﺑﺨـﺶﻫـﺎي Conclusion ،Results ،Methods ،Backgroundو Keywordsﺗﻨﻈـــﻴﻢ و در ﺣـــﺪود 240-250ﻛﻠﻤﻪ ﺑﺎﺷﺪ -3 .اﺻﻞ ﻣﻘﺎﻟﻪ ﺷﺎﻣﻞ ﻣﻮارد زﻳﺮ اﺳﺖ: ﻣﻘﺪﻣﻪ :ﻳﻚ ﺻﻔﺤﻪ ﺷﺎﻣﻞ -1 :اﻃﻼﻋﺎت ﻗﺒﻠﻲ و زﻣﻴﻨﻪاي اﻧﺠﺎم ﺷﺪه و ﺳﺎﺑﻘﻪ ﺑﺎ ذﻛﺮ رﻓﺮاﻧﺲ -2 .ﺿﺮورت اﻧﺠﺎم ﺗﺤﻘﻴﻖ -3 .ﺳﺆاﻻت ﺑﺪون ﭘﺎﺳﺨﻲ ﻛﻪ اﻳﻦ ﺗﺤﻘﻴﻖ ﺑﻪ آنﻫﺎ ﭘﺎﺳﺦ ﻣﻲﮔﻮﻳﺪ و ﺑﻴﺎن اﻳﻦ ﻣﻮﺿﻮع ﻛﻪ ﭼﮕﻮﻧﻪ ﻧﺘﺎﻳﺞ اﻳـﻦ ﺗﺤﻘﻴـﻖ ﻣـﻲﺗﻮاﻧـﺪ ﺑـﻪ رﻓـﻊ اﺑﻬﺎﻣﺎت ﻛﻤﻚ ﻛﻨﺪ -4 .ﺗﻌﺮﻳﻒ اﺻﻄﻼﺣﺎت ﺗﺨﺼﺼﻲ ﻳﺎ اﺧﺘﺼﺎرات ﻋﻠﻤﻲ -5 .ﻫﺪف ﺗﺤﻘﻴﻖ ﺑﻪ ﻧﺤﻮ روﺷﻦ.
آنﭼﻪ ﻛﻪ از اﻳﻦ ﺗﺤﻘﻴﻖ ﺑﻪ ﻋﻠﻢ اﺿﺎﻓﻪ ﺷﺪه اﺳﺖ. ﻣﻨﺎﺑﻊ :ﺷﻤﺎره ﻣﻨﺎﺑﻊ در ﻣﺘﻦ ﻗﻴﺪ ﺷﻮد و از ﻋﺪد ﻳﻚ ﺷﺮوع و ﺑﻪﺗﺮﺗﻴﺐ اﺿﺎﻓﻪ ﮔـﺮدد. ﺿﻤﻦ اﻧﻄﺒﺎق ﺗﻌﺪاد رﻓﺮاﻧﺲﻫﺎي ﻣﺤﺘﻮاي ﻣﻘﺎﻟﻪ و ﻟﻴﺴﺖ اﻧﺘﻬﺎﻳﻲ آن ،ﻣﺘﻦ رﻓـﺮاﻧﺲﻫـﺎ ﺑﻪﺗﺮﺗﻴﺐ ﻇﻬﻮر ،در ﻓﻬﺮﺳﺖ ﻣﻨﺎﺑﻊ آورده ﺷﻮﻧﺪ .ﻣﻨﺎﺑﻊ ﻓﺎرﺳـﻲ ﺑـﻪ اﻧﮕﻠﻴـﺴﻲ ﺑﺮﮔـﺮدان ﺷﻮد .ﻧﺤﻮه ﺗﻨﻈﻴﻢ ﻣﻨﺎﺑﻊ در ﻣﺜﺎلﻫﺎي زﻳﺮ آورده ﺷﺪه اﺳﺖ: 1. Qazi F, McGuire WP. The treatment of epithelial ovarian cancer. CA Cancer J Clin 1995;45(2):88-101. 2. Piazza AJ, Stoll BJ. Jaundice and hyperbilirobinemia in the newborn. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007. p. 756-65. 3. O'Callaghan C, Stephenson T. Pocket Paediatrics. 2nd ed. Edinburgh: Churchill Livingstone; 2004. 4. Williams FM, Cherkas LF, Spector TD, MacGregor AJ. A common genetic factor underlies hypertension and other cardiovascular disorders. BMC Cardiovasc Disord [Internet]. 2004 Apr 20 [cited 2009 Mar 23]; Available from: http://www.biomedcentral.com/1471-2261/4/20 5. Ghofranipour F, Shojaee zade D. Use of health belief model in prevention of ]brucelosis in Shahr-e-cord City in Iran. Daneshvar J 1997;15:23-8. [Persian
روش ﺑﺮرﺳﻲ :ﺑﻪﻧﺤﻮي ﺑﺎﻳﺪ ﻧﻮﺷﺘﻪ ﺷﻮد ﻛﻪ ﻫﺮ ﺧﻮاﻧﻨـﺪهاي ﺑﺘﻮاﻧـﺪ ﺑـﺎ آن ،ﺗﺠﺮﺑـﻪ
-3ﻧﺤﻮه ﺗﻨﻈﻴﻢ ﻣﻘﺎﻻت ﮔﺰارش ﻣﻮارد -1 :ﺻﻔﺤﻪ اول ﻣﺸﺎﺑﻪ ﻣﻘـﺎﻻت ﺗﺤﻘﻴﻘـﻲ-2 .
ﻧﻮﻳﺴﻨﺪه ﻣﻘﺎﻟﻪ را ﺗﻜﺮار ﻛﻨﺪ ،ﺷﺎﻣﻞ ﻃﺮاﺣﻲ ﺗﺤﻘﻴـﻖ :ﺟﺰﻳﻴـﺎت روش ﻣﻄﺎﻟﻌـﻪ و ﻋﻠـﺖ
ﺻﻔﺤﻪ دوم و ﺳﻮم ﺷﺎﻣﻞ ﺧﻼﺻﻪ ﻓﺎرﺳـﻲ و اﻧﮕﻠﻴـﺴﻲ و ﻛﻠﻤـﺎت ﻛﻠﻴـﺪي ﻓﺎرﺳـﻲ و
اﻧﺘﺨﺎب آن )ﻣﺜﻼ ﻛﻮﻫﻮرت( -ﻣﺪت زﻣﺎن اﺟﺮاي ﻃﺮح و ﭘﻲﮔﻴﺮي -1 .زﻣـﺎن و ﻣﻜـﺎن
اﻧﮕﻠﻴﺴﻲ ﻣﻲ ﺑﺎﺷﺪ .ﺧﻼﺻﻪ ﮔﺰارش ﻣﻮردي ﺣﺪاﻛﺜﺮ 130-150ﻛﻠﻤﻪ ﺑﺎﺷـﺪ -3 .اﺻـﻞ
اﺟﺮاي ﭘﮋوﻫﺶ -2 .ﺳﻮژهﻫـﺎ و ﻧﻤﻮﻧـﻪﻫـﺎي ﻣـﻮرد آزﻣـﻮن و ﻣـﻼك اﻧﺘﺨـﺎب .روش
ﻣﻘﺎﻟﻪ ﺷﺎﻣﻞ ﻣﻮارد زﻳﺮ اﺳﺖ :ﻣﻘﺪﻣﻪ :ﺷﺮح ﺣﺎل ﺑﻴﻤﺎر ،ﺑﺤﺚ :ﮔـﺰارش ﻣـﻮرد و ﺑﺤـﺚ
ﻧﻤﻮﻧﻪﮔﻴﺮي و ﻣﻨﻄﻖ ﺗﻌﺪاد ﻧﻤﻮﻧﻪ )اﻳﻦ ﻗﺴﻤﺖ ﺑﺴﻴﺎر ﻣﻬﻢ اﺳﺖ و در اﺑﺘﺪاي اﻣﺮ ﻣـﻮرد
ﻣﺠﻤﻮﻋﺎً از 1500ﻛﻠﻤﻪ ﺑﻴﺶﺗﺮ ﻧﺒﻮده و ﺣﺪاﻛﺜﺮ دو ﺟﺪول ﻳﺎ ﺗـﺼﻮﻳﺮ اراﻳـﻪ ﺷـﻮد-4 .
ﻛﺎرﺷﻨﺎﺳﻲ ﻗﺮار ﻣﻲﮔﻴﺮد( -ﻣﻼكﻫﺎي ورود و ﺧﺮوج ﺑﻪ ﻣﻄﺎﻟﻌﻪ -3 .ﻧﺤﻮه ﺟﻤـﻊآوري
ﻣﻨﺎﺑﻊ ﻣﺸﺎﺑﻪ ﻣﻘﺎﻻت ﺗﺤﻘﻴﻘﻲ اﺳﺖ.
اﻃﻼﻋــﺎت -4 .رﻋﺎﻳــﺖ ﻣــﻮازﻳﻦ اﺧــﻼق در ﭘــﮋوﻫﺶ -5 .اﺑﺰارﻫــﺎي اﻧــﺪازهﮔﻴــﺮي.
-4ﻧﺤﻮه ﺗﻨﻈﻴﻢ ﻣﻘﺎﻻت ﻣﺮوري -1 :اﻳﻦ ﻣﻘﺎﻻت ﺑﺮاي اراﻳﻪ آﺧﺮﻳﻦ ﻳﺎﻓﺘﻪﻫﺎي ﻋﻠﻤـﻲ
-6آزﻣﻮنﻫﺎي آﻣﺎري -7 .ﻧﺎم ﻛﺸﻮر و ﺷﺮﻛﺖ ﺳﺎزﻧﺪه ﻣﻮاد و دﺳﺘﮕﺎهﻫﺎ )ﺑﻪ اﻧﮕﻠﻴـﺴﻲ
درﺑﺎره ﻳﻚ ﻣﻮﺿﻮع ﺧﺎص ﺑﺎﺷﺪ -2 .ﻧﻮﻳﺴﻨﺪه در زﻣﻴﻨﻪ ﻣﻮﺿﻮع ﻣﻘﺎﻟﻪ ﺻـﺎﺣﺐ ﻧﻈـﺮ و
ﻧﻮﺷﺘﻪ ﺷﻮﻧﺪ(.
داراي ﻣﻘﺎﻟﻪ ﺑﺎﺷﻨﺪ -3 .از رﻓﺮﻧﺲﻫﺎي ﻧﻮﻳﺴﻨﺪه در ﻣﻘﺎﻟﻪ اﺳﺘﻔﺎده ﺷﺪه ﺑﺎﺷﺪ.
ﻳﺎﻓﺘﻪﻫﺎ :اراﻳﻪ ﻧﺘﺎﻳﺞ دﻗﻴﻖ -1 :رﻋﺎﻳـﺖ اﺻـﻮل ﻋﻠﻤـﻲ )ﮔـﺰارش ﻋـﺪد ﺑـﺎ درﺻـﺪ-
-5ﻫﻴﺄت ﺗﺤﺮﻳﺮﻳﻪ ﻣﺠﻠﻪ در ﻗﺒﻮل ﻳﺎ رد ،ﻳﺎ اﺻﻼح ﻣﻘﺎﻟﻪ )ﺑـﺎ ﺗﺄﻳﻴـﺪ ﻣﺆﻟـﻒ( آزاد
ﮔﺰارش ﻣﻴﺎﻧﮕﻴﻦ ﺑﺎ ﺣﺪود اﻃﻤﻴﻨﺎن -ﻣﻴﺎﻧﻪ ﺑـﺎ -2 .(Rangeﭘﺮﻫﻴـﺰ از ﻧـﺸﺎن دادن ﻫﻤـﻪ
اﺳﺖ و از ﭘﺲ دادن ﻣﻘﺎﻟﻪ و ﻣﻠﺤﻘﺎت آن ﻣﻌﺬور ﻣﻲﺑﺎﺷﺪ.
ﻳـﺎﻓﺘﻪﻫﺎي ﺑﻪدﺳﺖ آﻣﺪه ﺑﻪﺟﺰ ﻳـﺎﻓﺘﻪﻫﺎي ﻣﻬﻢ و ﺗﻌﻴـﻴﻦﻛﻨﻨـﺪه -3 .اﺳﺘــﻔﺎده ﻣﻨــﺎﺳﺐ
-6ﻧﻮﻳﺴﻨﺪﮔﺎن ﻣﻘﺎﻻت ﻣﺴﺌﻮل ﻧﻮﺷﺘﻪﻫﺎ و ﻣﺪاﻓﻊ ﻣﻄﺎﻟﺐ ﭼﺎپ ﺷﺪه از ﻣﻘﺎﻟﻪ ﺧـﻮد در
از ﺟﺪول و ﻧﻤﻮدار ﺑﺎ ﺣﺪاﻗﻞ ﺗﻌﺪاد ﻣﻤﻜﻦ ﺑﻪﻃﻮريﻛﻪ ﺑﻪ ازاي ﻫﺮ ﺳـﻪ ﺻـﻔﺤﻪ ﺗـﺎﻳﭙﻲ
ﻣﺠﻠﻪ ﺧﻮاﻫﻨﺪ ﺑﻮد.
ﻳﻚ ﺟﺪول ﻳﺎ ﻧﻤﻮدار اﺳﺘﻔﺎده ﺷﻮد ،ﺿﻤﻦ اﻳﻦﻛﻪ ﻧﻤﻮدار ﺑﺎﻳﺪ ﺳﻴﺎه و ﺳﻔﻴﺪ و دو ﺑﻌﺪي
-7اﺳﺘﻔﺎده از ﻣﻨﺪرﺟﺎت ﻣﺠﻠﻪ ﺑﺎ ذﻛﺮ ﻛﺎﻣﻞ ﻣﺄﺧﺬ آزاد اﺳﺖ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ، 70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
77ي69- ،1391 ﺷﻤﺎره ،2 70ﻳ، ، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ، داﻧﺸﻜﺪه ﻣﺠﻠﻪ ﻛﻠﻴﻮ اردﻳﺒﻬﺸﺖﻣﺠﺪد ﺧﻮنرﺳﺎﻧﻲ ﺴﻜﻤﻲ- دوره ﺑﺎ ا ﺗﻬﺮان،ﻣﻮش ﭘﺰﺷﻜﻲﺖﻫﺎ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴ ﺮﻧﺪه ﭘﺲ از ﻛﻠﻴﻮي ﭘﺬﻳ آﺳﻴﺐ
69
ﺑﺮرﺳﻲ آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘﺲ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ از ﻣﻮش ﺳﻮري Inbredﻣﺒﺘﻼ ﺑﻪ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﻛﻠﻴﻮي
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/06/08 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/03 :
ﭼﻜﻴﺪه
*1
ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ
1
2
ﺣﺴﻴﻦ ﺧﻮاﺳﺘﺎر ،ﺑﻬﺠﺖ ﺳﻴﻔﻲ 1
ﻋﺎﻃﻔﻪ ﻧﺠﻔﻲ 3،ﻓﺎﻃﻤﻪ دﻻوري
زﻣﻴﻨﻪ و ﻫﺪف :در ﻣﻄﺎﻟﻌﻪ ﻗﺒﻠﻲ ﻣﺎ ﻧﻘﺶ اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ را در اﻟﻘﺎي آﺳﻴﺐ ﻛﺒﺪي ﺑـﻪدﻧﺒـﺎل اﻳـﺴﻜﻤﻲ -ﺧـﻮنرﺳـﺎﻧﻲ ﻣﺠﺪد ) (IRﻛﻠﻴﻮي در ﻣﻮش ﺳﻮري Inbredﻧﺸﺎن داده ﺷﺪ .ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ ﻧﻘﺶ اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ را از ﻣﻮش ﻣﺒـﺘﻼ ﺑـﻪ
-1ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان. -2ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺷﺎﻫﺮود ،ﺷﺎﻫﺮود ،اﻳﺮان.
آﺳﻴﺐ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ) 60دﻗﻴﻘﻪ اﻧﺴﺪاد دو ﻃﺮﻓﻪ ﺷﺮﻳﺎن ﻛﻠﻴﻮي و ﺳﻪ ﺳﺎﻋﺖ ﭘﺮﻓﻴﻮژن ﻣﺠـﺪد( در اﻳﺠـﺎد آﺳﻴﺐ ﻛﻠﻴﻮي در ﻣﻮش ﭘﺬﻳﺮﻧﺪه ﺑﺮرﺳﻲ ﻣﻲﻧﻤﺎﻳﺪ .روش ﺑﺮرﺳﻲ :ﻣﻮشﻫﺎ در دو ﮔﺮوه Shamو IRﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﭘﺲ از ﺑﻴﻬﻮﺷﻲ و ﺑﺮداﺷﺖ ﺧﻮن و ﺑﺎﻓﺖ ﻛﻠﻴﻮي ،ﻟﻜﻮﺳﻴﺖﻫﺎ از ﺧﻮن ﺟﺪا ﺷﺪه و ﺑﻪ دو ﮔﺮوه ﭘﺬﻳﺮﻧﺪه ﻣﻨﺘﻘﻞ ﺷﺪﻧﺪ :ﻣﻮشﻫـﺎي )recipient
(Shamو ﻣﻮشﻫﺎي ﭘﺬﻳﺮﻧﺪه ﻛﻪ ﻟﻜﻮﺳﻴﺖﻫـﺎي ﮔـﺮوه
-3ﮔﺮوه آﻧﺎﺗﻮﻣﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،
ﭘﺬﻳﺮﻧﺪه ﻛﻪ ﻟﻜﻮﺳﻴﺖﻫﺎي ﮔﺮوه ﺷﻢ را درﻳﺎﻓﺖ ﻛﺮدﻧﺪ
ﺗﻬﺮان ،اﻳﺮان.
IRرا درﻳﺎﻓﺖ ﻧﻤﻮدﻧﺪ ) .(IR recipientﺑﻌﺪ از 24ﺳﺎﻋﺖ ﻧﻤﻮﻧﻪﻫﺎي ﺧﻮن و ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﺟﻤﻊآوري ﺷﺪ .ﻳﺎﻓﺘﻪﻫﺎ :در ﮔﺮوه recipient
IRﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه
recipient
Shamﻣﻴﺰان ﻣﺎﻟﻮن دي آﻟﺪﻫﺎﻳﺪ ) (MDAﺑﺎﻓﺖ ﻛﻠﻴﻪ ﺑﻪﻃـﻮر ﻣﻌﻨـﻲدار اﻓـﺰاﻳﺶ و
ﮔﻠﻮﺗﺎﺗﻴﻮن و ﺳﻮﭘﺮاﻛﺴﻴﺪ دﻳﺴﻤﻮﺗﺎز ﻛﺎﻫﺶ ﻳﺎﻓﺘﻨﺪ Blood Urea Nitrogen (BUN) .و ﻛﺮآﺗﻴﻨﻴﻦ ﭘﻼﺳﻤﺎ اﮔﺮﭼﻪ در ﮔﺮوه
IR
donorﺑﺎ ﺷﻢ ﺗﻔﺎوت ﻣﻌﻨﻲداري داﺷﺖ ) (P<0/05وﻟﻲ در دو ﮔﺮوه ﭘﺬﻳﺮﻧﺪه ﺗﻔﺎوت ﻣﻌﻨﻲدار وﺟﻮد ﻧﺪاﺷﺖ .ﺑﺎﻓـﺖ ﻛﻠﻴـﻪ در ﮔﺮوه IR donorدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorآﺳﻴﺐﻫﺎي ﺑﺴﻴﺎري را ﻧﺸﺎن داد .اﻣﺎ ﮔـﺮوه IR recipientاﮔﺮﭼـﻪ ﺑـﺎ *
ﮔﺮوه ﺷﻢ ﻣﺮﺑﻮﻃﻪ ﺑﺴﻴﺎر ﻣﺘﻔﺎوت اﺳﺖ وﻟﻲ ﺑﺎ ﮔﺮوه IR donorﻫﻢ ﺗﻔـﺎوت ﺑـﺴﻴﺎري دارد .ﻧﺘﻴﺠـﻪﮔﻴـﺮي :اﻳـﻦ ﻳﺎﻓﺘـﻪﻫـﺎ ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،ﺧﻴﺎﺑﺎن ﭘﻮرﺳﻴﻨﺎ ،داﻧﺸﮕﺎه ﻋﻠﻮم
ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي
ﻟﻜﻮﺳﻴﺖﻫﺎ را ﺑﻪ ﻋﻨﻮان ﻳﻚ ﻋﺎﻣﻞ دﺧﻴﻞ در آﺳﻴﺐ ﺑﺎﻓﺘﻲ و اﻟﻘﺎي اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ در آﺳﻴﺐ IRﻛﻠﻴﻪ ﻣﻄﺮح ﻣﻲﻧﻤﺎﻳﺪ.
ﺗﻠﻔﻦ021-64053288 : E-mail: kadkhodm@tums.ac.ir
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﻛﻠﻴﻪﻫﺎ ،آﺳﻴﺐ اﻳﺴﻜﻤﻲ ،ﭘﺮﻓﻴﻮژن ﻣﺠﺪد ،ﻟﻜﻮﺳﻴﺖﻫﺎ ،اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ.
ﺑﻪﺧﺼﻮص ،TNF-αﺧﻮد ﺑﺎ ﻓﻌﺎل ﻛﺮدن ﻟﻜﻮﺳـﻴﺖﻫـﺎ ﻧﻘـﺶ ﻣﻬﻤـﻲ در
ﻣﻘﺪﻣﻪ
ﮔﺴﺘﺮش آﺳﻴﺐ ﻧﺎﺷﻲ از اﻳﺴﻜﻤﻲ دارﻧـﺪ5.و 4آﺳـﻴﺐ ﻧﺎﺷـﻲ از IRﻳـﻚ )Ischemia-Reperfusion (IR
اﻧﺪام ﻣﻮﺟﺐ ﭘﺎﺳﺦ اﻟﺘﻬﺎﺑﻲ ﺳﻴﺴﺘﻤﻴﻚ ﻣﻲﮔﺮدد ﻛﻪ در ﻧﺘﻴﺠﻪ آن آﺳـﻴﺐ
ﻛﻠﻴﻮي در ﺑﺴﻴﺎري از ﻣﻮارد ﻛﻠﻴﻨﻴﻜﻲ ﻣﺎﻧﻨﺪ ﺷﻮك ،ﭘﻴﻮﻧﺪ اﻋﻀﺎ ،ﻋﻔﻮﻧـﺖ
در اﻧﺪامﻫﺎي دور دﺳﺖ دﻳﮕـﺮ ﻣﺎﻧﻨـﺪ ﻗﻠـﺐ ،رﻳـﻪ ،روده و ﻛﺒـﺪ اﻳﺠـﺎد
آﺳﻴﺐ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد
و ﺟﺮاﺣﻲﻫﺎي ﻋﺮوق اﻳﺠﺎد ﻣﻲﺷﻮد ﻛﻪ در ﻧﻬﺎﻳﺖ ﻣـﻲﺗﻮاﻧـﺪ ﻣﻨﺠـﺮ ﺑـﻪ
ﻣﻲﺷﻮد .ﻣﻄﺎﻟﻌﺎت اﭘﻴﺪﻣﻴﻮﻟﻮژﻳﻚ ﻧـﺸﺎن ﻣـﻲدﻫـﺪ ﻛـﻪ IRﻛﻠﻴـﻮي ﻧﻴـﺰ
ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴﻮي ) (ARFو ﻣـﺮگ و ﻣﻴـﺮ ﻗﺎﺑـﻞ ﺗﻮﺟـﻪ ﻧﺎﺷـﻲ از آن
6-8
ﻣﻮﺟﺐ اﺧﺘﻼل در اﻧﺪامﻫﺎي دﻳﮕﺮ ﻣﺎﻧﻨﺪ ﻣﻐﺰ ،رﻳﻪ و ﻛﺒـﺪ ﻣـﻲﮔـﺮدد.
ﮔﺮدد ،ﭼﻨﺎنﻛﻪ ﻋﻠﻲرﻏﻢ ﭘﻴﺸﺮﻓﺖ ﺑﺴﻴﺎر در اﻣﺮ ﭘﻴﻮﻧﺪ ﻛﻠﻴﻪ ،ﻣﺮگ و ﻣﻴـﺮ
در ﻣﻮرد ﻧﻘﺶ IRﻛﻠﻴﻮي در آﺳﻴﺐ اﻧﺪامﻫﺎي دوردﺳﺖ ﻣﻄﺎﻟﻌﺎت ﺑﺴﻴﺎر
1
اﻧﺪﻛﻲ اﻧﺠﺎم ﺷﺪه ﻛﻪ ﺻﺮﻓﺎً وﺟﻮد آﺳﻴﺐ را در آن اﻧﺪام ﻧـﺸﺎن دادهاﻧـﺪ
ﭘﻴﺸﻨﻬﺎد ﺷﺪه ﻛﻪ IRﻛﻠﻴﻮي ﻣﻮﺟـﺐ اﻟﻘـﺎ ﺗﻮﻟﻴـﺪ ﺳـﺎﻳﺘﻮﻛﻴﻦﻫـﺎي ﭘـﻴﺶ
وﻟﻲ ﻣﻜﺎﻧﻴﺴﻢ اﻳﺠﺎد ﺿﺎﻳﻌﻪ ﺑﺮرﺳﻲ ﻧﺸﺪه اﺳﺖ .ﺑـﺎ ﺗﻮﺟـﻪ ﺑـﻪ ﺷـﻴﻮع و
اﻟﺘﻬﺎﺑﻲ ﻣﺎﻧﻨﺪ ،TNF-αﺑﻴﺎن ﻣﻮﻟﻜﻮلﻫﺎي ﭼﺴﺒﻨﺪه ﮔﻮﻧﺎﮔﻮن ،ﻓﻌـﺎل ﺷـﺪن
ﻣﺨﺎﻃﺮهﻫﺎي IRﻛﻠﻴﻮي و ﺑـﻪدﻟﻴـﻞ اﻫﻤﻴـﺖ ﻛﻠﻴـﻪ در ﺣﻔـﻆ ﺳـﻼﻣﺖ و
ﻟﻜﻮﺳﻴﺖﻫﺎ و ورود آنﻫﺎ ﺑﻪ داﺧﻞ ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﻣﻲﺷﻮد3و 2و ﺳﺎﻳﺘﻮﻛﻴﻦﻫﺎ
ﻧﮕﻪداري ﺛﺒﻮت ﻣﺤﻴﻂ داﺧﻠـﻲ ﺑـﺪن ،ﺑﺮرﺳـﻲ ﻣﻜﺎﻧﻴـﺴﻢ IRﻛﻠﻴـﻮي در
) (Mortalityﺑﻴﻤﺎران ﺑﻪ ﻋﻠﺖ آﺳﻴﺐ ﻛﻠﻴﻮي ﻫـﻢﭼﻨـﺎن ﺑـﺎﻻ ﻣـﻲﺑﺎﺷـﺪ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ و ﻫﻤﻜﺎران
70
اﻳﺠﺎد آﺳﻴﺐﻫﺎي ﻣﻮﺿﻌﻲ دوردﺳﺖ ) (Remoteداراي اﻫﻤﻴـﺖ ﺧﺎﺻـﻲ
ﺣﻴﻮاﻧﺎت ﮔﺮﻓﺘﻪ ﺷﺪه و ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﻧﻴﺰ ﺟﻤـﻊآوري ﺷـﺪ .ﻣﻴـﺰان BUNو
IR
ﻛــﺮاﺗﻴﻨﻴﻦ ﭘﻼﺳــﻤﺎ ﺑــﻪﻋﻨــﻮان ﺷــﺎﺧﺺﻫــﺎي آﺳــﻴﺐ ﻋﻤﻠﻜــﺮد ﻛﻠﻴــﻮي
اﻧﺪامﻫﺎي ﻣﺨﺘﻠﻒ ﻣﺎﻧﻨﺪ رﻳﻪ ،ﻗﻠﺐ ،ﻣﻐﺰ ،ﻛﻠﻴﻪ ،ﻛﻮﻟﻮن و ﻛﺒـﺪ ﺑﺮرﺳـﻲ و
اﻧﺪازهﮔﻴﺮي ﺷﺪ .ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﺑﺮاي ﺑﺮرﺳﻲ ﺑﺎﻓﺖﺷﻨﺎﺳـﻲ و اﻧـﺪازهﮔﻴـﺮي
ﺗﺄﻳﻴﺪ ﻛﺮدهاﻧﺪ 9-11.در ﻳﻚ ﻣﻄﺎﻟﻌﻪ اﺧﻴﺮ ﻣـﺎ ﻣﻮﻓـﻖ ﺷـﺪﻳﻢ ﻧﻘـﺶ اﻧﺘﻘـﺎل
ﺷﺎﺧﺺﻫﺎي اﻛﺴﻴﺪاﺗﻴﻮ ﺧﺎرج ﺷﺪه و ﭘﺲ از ﺷﺴﺘﺸﻮ در ﻣﺤﻠـﻮل ﺑـﺎﻓﺮ
ﻟﻜﻮﺳﻴﺖﻫﺎ را در اﻟﻘﺎي آﺳﻴﺐ ﻛﺒﺪي ﺑﻪدﻧﺒﺎل اﻳﺴﻜﻤﻲ -ﭘﺮﻓﻴﻮژن ﻣﺠﺪد
ﻓﺴﻔﺎت ﺳﺎﻟﻴﻦ ) (PBSﺑﻪ دو ﺑﺨﺶ ﺗﻘﺴﻴﻢ ﮔﺮدﻳﺪ ﻛﻪ ﻧﻴﻤﻲ از آن ،ﺟﻬﺖ
ﻛﻠﻴﻮي در ﻣﻮش ﺳﻮري Inbredﻧﺸﺎن دﻫـﻴﻢ 12.ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ ﻧﻘـﺶ
آزﻣﺎﻳﺸﺎت ﺑﺎﻓﺖﺷﻨﺎﺳﻲ در ﻣﺤﻠﻮل ﻓﺮﻣﺎﻟﻴﻦ %10ﻓﻴﻜﺲ ﮔﺮدﻳﺪه و ﻧـﻴﻢ
اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ را از ﻣـﻮش ﻣﺒـﺘﻼ ﺑـﻪ آﺳـﻴﺐ IRﻛﻠﻴـﻮي در اﻳﺠـﺎد
دﻳﮕﺮ ﺑﺮاي ﺗﻌﻴﻴﻦ ﻣﻴﺰان ﻣﺎﻟﻮن دي آﻟﺪﻫﺎﻳﺪ
)Malondialdehyde (MDA
آﺳﻴﺐ ﻛﻠﻴﻮي در ﻣﻮش ﭘﺬﻳﺮﻧﺪه ﺑﺮرﺳﻲ ﻣﻲﻧﻤﺎﻳﺪ .در اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﭘـﺲ
و ﺳـﻮﭘﺮ اﻛـﺴﺎﻳﺪ دﻳـﺴﻤﻮﺗﺎز ) Superoxide Dismutase (SODﻛﺎﺗـﺎﻻز،
از 60دﻗﻴﻘﻪ اﻳﺴﻜﻤﻲ دوﻃﺮﻓﻪ ﺷﺮﻳﺎن ﻛﻠﻴﻮي و ﺧﻮنرﺳﺎﻧﻲ ﻣﺠـﺪد ﺳـﻪ
ﮔﻠﻮﺗﺎﺗﻴﻮن ﺗﻮﺗﺎل و ) Ferric Reducing Antioxidant Power (FRAPﺗـﺎ
ﻣﻲﺑﺎﺷﺪ .ﺳﺎﻟﻴﺎن زﻳﺎدي اﺳﺖ ﻛﻪ ﻧﻘﺶ ﻟﻜﻮﺳﻴﺖﻫـﺎ را در ﺿـﺎﻳﻌﺎت
ﺳﺎﻋﺘﻪ ﻧﻤﻮﻧﻪ ﺧﻮن ﻣﺤﻴﻄﻲ از ﻣﻮشﻫﺎ ﮔﺮﻓﺘﻪ و ﺳﭙﺲ ﻟﻜﻮﺳﻴﺖﻫـﺎي آن
روز آﻧﺎﻟﻴﺰ در
C
°
-70ﻧﮕﻪداري ﺷﺪ.
اﻳﺰوﻟﻪ و ﺑﻪ ﻣﻮشﻫﺎي ﺳﺎﻟﻢ ﺗﺰرﻳﻖ ﺷـﺪ ﺗـﺎ اﺛـﺮ اﻳـﻦ ﻟﻜﻮﺳـﻴﺖﻫـﺎ ﺑـﺮ
آﻣــﺎدهﺳــﺎزي و اﻧﺘﻘــﺎل ﻟﻜﻮﺳــﻴﺖﻫــﺎ ﺑــﻪ ﻣــﻮشﻫــﺎي ﭘﺬﻳﺮﻧــﺪه
وﺿﻌﻴﺖ ﻋﻤﻠﻜﺮدي ،ﺑﺎﻓﺘﻲ و اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ ﻛﻠﻴﻪ ﻣﻮشﻫـﺎي ﺳـﺎﻟﻢ
) :(Recipientﻧﻤﻮﻧﻪ ﺧﻮن ﺟﻤﻊآوري ﺷﺪه از ﻗﻠﺐ ﻣﻮشﻫﺎي ﮔﺮوهﻫﺎي C
°
4
ﻧﺸﺎن داده ﺷﻮد .ﻧﺘﺎﻳﺞ اﻳﻦ ﭘﮋوﻫﺶ ﺑﻪﻃﻮر اﺧﺘﺼﺎﺻﻲ ﻧﻘﺶ ﻟﻜﻮﺳﻴﺖﻫﺎ
دﻫﻨــﺪه )ﻳــﻚ و دو( ﺑــﻪ ﻣــﺪت 10دﻗﻴﻘــﻪ در 4000دور در
را در اﻳﺠﺎد آﺳﻴﺐ ﻛﻠﻴﻪ ﺑﻪدﻧﺒﺎل IRﻛﻠﻴﻮي ارزﻳﺎﺑﻲ ﻣﻲﻛﻨﺪ.
ﺳـﺎﻧﺘﺮﻳﻔﻮژ ﺷـﺪ .ﺑﻌـﺪ از ﺑﺮداﺷـﺘﻦ ﭘﻼﺳـﻤﺎ ،ﺑـﻪ ﺑﺎﻗﻴﻤﺎﻧـﺪه ﺟﻬـﺖ ﻟﻴــﺰ ارﻳﺘﺮوﺳﻴﺖﻫﺎ ﺑﻪ ﻧﺴﺒﺖ ﻳﻚ ﺑﻪ 10ﻣﺤﻠﻮل ﻛﻠﺮﻳﺪ آﻣﻮﻧﻴﻮم اﺿﺎﻓﻪ و ﭘـﻨﺞ دﻗﻴﻘﻪ در دﻣﺎي اﺗﺎق ﻧﮕﻪداري ﺷﺪ .ﺳﭙﺲ ﺑﺮاي ﺧﺘﻢ واﻛﻨﺶ 20اﻟﻲ 30
روش ﺑﺮرﺳﻲ
ﻣﻴﻠﻲﻟﻴﺘﺮ ﺑـﺎﻓﺮ ﻓـﺴﻔﺎت ﺑـﻪ آن اﺿـﺎﻓﻪ و ﺑﻌـﺪ از ﺳـﺎﻧﺘﺮﻳﻔﻮژ ﻣﺠـﺪد در
اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﻨﻴﺎدي در ﺳﺎل 1389در ﮔـﺮوه ﻓﻴﺰﻳﻮﻟـﻮژي داﻧـﺸﻜﺪه
،1200rpmﻟﻜﻮﺳﻴﺖﻫﺎي ﺗﻪﻧﺸﻴﻦ ﺷﺪه دو ﺑﺎر ﺑﺎ ﺑﺎﻓﺮ ﻓﺴﻔﺎت ﺷﺴﺘـﺸﻮ
ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ﺑﻪ اﻧﺠﺎم رﺳﻴﺪه اﺳﺖ .ﺗﻌـﺪاد 32
داده ﺷﺪ .رﺳﻮب ﺑﺎ 500ﻣﻴﻜﺮوﻟﻴﺘﺮ ﻧﺮﻣﺎل ﺳﺎﻟﻴﻦ رﻗﻴﻖ ﺷﺪه و در واﺣﺪ
ﺳﺮ ﻣﻮش ﺳﻮري BALB/cﻧﺮ در ﻣﺤﺪوده وزﻧﻲ 25-35ﮔـﺮم ﺑـﻪﻃـﻮر
(Trypan blue exclusion
ﺣﺠﻢ ﺑﺎ ﺗﻜﻨﻴـﻚ رﻧـﮓآﻣﻴـﺰي ﺗﺮﻳﭙـﺎن ﺑﻠـﻮ 6
(IR
ﺗﺼﺎدﻓﻲ اﻧﺘﺨﺎب و ﺑﻪ ﭼﻬﺎر ﮔﺮوه ﻫﺸﺖ ﺗﺎﻳﻲ ﺗﻘﺴﻴﻢ ﺷـﺪﻧﺪ -1 :ﮔـﺮوه
) techniqueﺷــﻤﺎرش ﮔﺮدﻳــﺪ 5×10 .ﻟﻜﻮﺳــﻴﺖ از ﮔــﺮوه ﻳــﻚ
،IRدﻫﻨﺪه ﻟﻜﻮﺳـﻴﺖ ) -2 .(IR donorﮔـﺮوه ،Shamدﻫﻨـﺪه ﻟﻜﻮﺳـﻴﺖ
) donorﺑﻪ ﮔﺮوه ﺳﻪ ) (IR recipientو ﻫﻤﻴﻦ ﺗﻌﺪاد ﻟﻜﻮﺳـﻴﺖ از ﮔـﺮوه
IR donor
دو ) (Sham donorﺑﻪ ﮔﺮوه ﭼﻬﺎر ) (Sham recipientﺗﻮﺳﻂ ﺗﺰرﻳـﻖ از
) -3 .(Sham donorﮔــﺮوه درﻳﺎﻓــﺖﻛﻨﻨــﺪه ﻟﻜﻮﺳــﻴﺖ از ) -4 .(IR recipientﮔــﺮوه درﻳﺎﻓــﺖﻛﻨﻨــﺪه ﻟﻜﻮﺳــﻴﺖ از
Sham donor
راه ورﻳﺪ دﻣﻲ اﻧﺘﻘﺎل داده ﺷﺪ.
) .(Sham recipientدو ﮔﺮوه اول ﻣﻮشﻫﺎ ﺗﻮﺳﻂ ﺗﺰرﻳﻖ داﺧﻞ ﺻـﻔﺎﻗﻲ
روش ﻧﻤﻮﻧﻪﮔﻴﺮي از ﺣﻴﻮاﻧﺎت ﭘﺬﻳﺮﻧﺪه ﻟﻜﻮﺳﻴﺖﻫﺎ :ﺣﻴﻮاﻧﺎت ﭘـﺲ
(60mg/kg ،Sigma, Co,ﺑﻴﻬـﻮش ﺷـﺪﻧﺪ .در
از ﻣــﺪت 24ﺳــﺎﻋﺖ ﺑــﺎ ﺗﺰرﻳــﻖ داﺧــﻞ ﺻــﻔﺎﻗﻲ ﭘﻨﺘﻮﺑﺎرﺑﻴﺘــﺎل ﺳــﺪﻳﻢ
ﺗﻤﺎم اﻳﻦ ﻣﺪت درﺟﻪ ﺣﺮارت ﺑﺪن ﺣﻴﻮان ﻛﻨﺘﺮلﺷﺪه و ﻓـﺸﺎر ﺷـﺮﻳﺎﻧﻲ
) (60mg/kgﺑﻴﻬﻮش ﺷﺪﻧﺪ و ﻧﻤﻮﻧـﻪ ﺧـﻮن ورﻳـﺪي از ورﻳـﺪ اﺟـﻮف
ﺗﻮﺳﻂ Tail cuffاﻧﺪازهﮔﻴﺮي ﺷﺪ .ﺳﭙﺲ ﺗﺤﺖ ﺷﺮاﻳﻂ اﺳـﺘﺮﻳﻞ ﺑﺮﺷـﻲ
ﺗﺤﺘﺎﻧﻲ ﺑﻪ ﻣﻨﻈﻮر اﻧﺪازهﮔﻴﺮي ﺷﺎﺧﺺﻫﺎي ﻋﻤﻠﻜﺮدي ﻛﻠﻴﻪ ﮔﺮﻓﺘﻪ ﺷـﺪ.
در ﺧﻂ وﺳﻂ روي ﺷﻜﻢ اﻳﺠﺎد ﮔﺮدﻳﺪ .در ﮔﺮوه ،IR donorﺑﺎ اﺳـﺘﻔﺎده
ﺳﭙﺲ ﻛﻠﻴﻪ ﭼـﭗ در آورده ﺷـﺪ و ﭘـﺲ از ﺷﺴﺘـﺸﻮ در ﻣﺤﻠـﻮل ﺑـﺎﻓﺮ
از ﻛﻠﻤﭗ ﺑﻮﻟﺪاگ 60دﻗﻴﻘﻪ اﻳﺴﻜﻤﻲ دوﻃﺮﻓﻪ ﺷﺮﻳﺎن ﻛﻠﻴﻮي داده ﺷﺪ و
ﻓﺴﻔﺎت ﺳﺎﻟﻴﻦ ) (PBSﻗﺴﻤﺘﻲ از ﻛﻠﻴﻪ ﺑﺮاي ﺑﺮرﺳﻲﻫـﺎي ﻣﻮرﻓﻮﻟﻮژﻳـﻚ
ﭘﺲ از آن ﺳﻪ ﺳﺎﻋﺖ ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﺑﺮﻗـﺮار ﮔﺮدﻳـﺪ .ﺗﻐﻴﻴـﺮ رﻧـﮓ
در ﻓﺮﻣﺎﻟﻴﻦ %10ﻓﻴﻜﺲ ﮔﺮدﻳﺪ .ﺑﻘﻴﻪ آن ﺑﺮاي ﻳﺦ زدﮔﻲ ﺳﺮﻳﻊ ﺑﻼﻓﺎﺻﻠﻪ
ﻛﻠﻴﻪﻫﺎ ﻧﺸﺎنﮔﺮ ﺗﺎﻳﻴﺪ و رﻓﻊ اﻧﺴﺪاد ﺷﺮﻳﺎن ﻛﻠﻴﻮي ﻣـﻲﺑﺎﺷـﺪ .در ﮔـﺮوه
ﺑﻪداﺧـﻞ ﻧﻴﺘـﺮوژن ﻣـﺎﻳﻊ ﮔﺬاﺷـﺘﻪ ﺷـﺪ و ﺳـﭙﺲ ﺟﻬـﺖ اﻧـﺪازهﮔﻴـﺮي
ﭘﻨﺘﻮﺑﺎرﺑﻴﺘﺎل ﺳﺪﻳﻢ
)USA
C
°
-70
Sham donorﻧﻴﺰ ﺗﻤﺎم اﻋﻤﺎل ﺟﺮاﺣﻲ ﻓﻮق اﻧﺠﺎم ﺷـﺪه اﻣـﺎ ﺷـﺮﻳﺎنﻫـﺎ
ﺷﺎﺧﺺﻫـﺎي ذﻛـﺮ ﺷـﺪه در ﺑـﺎﻻ ﺗـﺎ زﻣـﺎن آﻧـﺎﻟﻴﺰ در ﻓﺮﻳـﺰر
ﻛﻠﻤــﭗ ﻧﮕﺮدﻳـﺪ .در اﻧﺘﻬــﺎي آزﻣــﺎﻳﺶ ﻧﻤﻮﻧــﻪ ﺧــﻮن ﻣﺤﻴﻄــﻲ از ﻗﻠــﺐ
ﻧﮕﻪداري ﺷﺪ .ﺑﺮاي ﺗﻬﻴﻪ ﭘﻼﺳﻤـﺎ ،ﻧﻤﻮﻧـﻪﻫـﺎي ﺧـﻮن ﺑـﺎ دور 4000ﺑﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘﺲ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ از ﻣﻮش ﺑﺎ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﻛﻠﻴﻮي
Reperfusion
Ischemia IR group 60 min
3 hrs
71
ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴـﻪ اﻳـﺴﻜﻤﻴﻚ ﺳـﺒﺐ اﻟﻘـﺎي آﺳـﻴﺐ ﻋﻤﻠﻜـﺮدي ﻛﻠﻴـﻪ ﮔﺮدﻳــﺪ .در ﮔــﺮوهﻫــﺎي IR recipientو Sham recipientﺗﻔــﺎوت
Sham group 4 hrs
ﻣﻌﻨﻲداري در ﻏﻠﻈﺖ ﭘﻼﺳﻤﺎﻳﻲ BUNﻣﻼﺣﻈﻪ ﻧﺸﺪ )ﻧﻤﻮدار .(1b ﻏﻠﻈﺖ ﻛﺮاﺗﻴﻨﻴﻦ ﭘﻼﺳﻤﺎ در ﮔﺮوه IR donorاﻓﺰاﻳﺶ ﻣﻌﻨـﻲداري در
WBC receptive groups WBC transfer
24 hrs
Time
ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorداﺷﺖ )ﻧﻤـﻮدار .(1aاﻓـﺰاﻳﺶ ﻛـﺮاﺗﻴﻨﻴﻦ ﻧﺸﺎندﻫﻨﺪه آﺳﻴﺐ ﻋﻤﻠﻜﺮدي ﻛﻠﻴـﻪ در ﮔـﺮوه IR donorﻣـﻲﺑﺎﺷـﺪ .در
ﺧﻼﺻﻪ ﻣﺮاﺣﻞ ﻣﻄﺎﻟﻌﻪ ﻛﻪ زﻣﺎن اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ ﺑﻪ ﻣﻮشﻫﺎي ﺳﺎﻟﻢ و ﺧﺎﺗﻤﻪ
ﮔــﺮوهﻫــﺎي IR recipientو Sham recipientﺗﻔــﺎوت ﻣﻌﻨــﻲداري در
ﭘﺮوﺗﻜﻞ و زﻣﺎن ﻧﻤﻮﻧﻪﮔﻴﺮي را ﻧﺸﺎن ﻣﻲدﻫﺪ.
ﻏﻠﻈﺖ ﭘﻼﺳﻤﺎﻳﻲ ﻛﺮاﺗﻴﻨﻴﻦ ﻣﻼﺣﻈﻪ ﻧﺸﺪ )ﻧﻤﻮدار .(1b ﺑﺮرﺳﻲ ﺗﻐﻴﻴﺮات ﺷﺎﺧﺺﻫﺎي اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ ﻛﻠﻴﻪ در ﮔﺮوهﻫـﺎ: ﻣﻴﺰان ﻣﺎﻟﻮن ديآﻟﺪﻫﺎﻳﺪ ) (MDAدر ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﮔﺮوه IR donorاﻓﺰاﻳﺶ
ﻣﺪت 10دﻗﻴﻘﻪ در دﻣﺎي 0-4 °Cﺳﺎﻧﺘﺮﻳﻔﻮژ ﺷﺪ .ﺗﻤﺎم ﻧﻤﻮﻧﻪﻫﺎ ﺗﺎ زﻣﺎن
ﻣﻌﻨﻲداري در ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorداﺷـﺖ )ﻧﻤـﻮدار .(2aﺑـﻪ
آﻧﺎﻟﻴﺰ در ﻓﺮﻳﺰر -70 °Cﻧﮕﻪداري ﺷﺪﻧﺪ.
اﻳﻦ ﺗﺮﺗﻴﺐ در اﻳﻦ ﺗﺤﻘﻴﻖ ﻣﻴﺰان MDAﺑﻪ ﻋﻨﻮان ﺷﺎﺧﺺ اﻳﺠﺎد اﺳﺘﺮس
ﺑﺮرﺳــﻲ ﺗﻐﻴﻴــﺮات ﻓــﺸﺎر ﺳﻴــﺴﺘﻮﻟﻴﻚ :در ﻃــﻲ ﺟﺮاﺣــﻲ ﻓــﺸﺎر ﺳﻴﺴﺘﻮﻟﻴﻚ و ﺿﺮﺑﺎن ﻗﻠـﺐ در ﮔـﺮوه IR donorو
ﮔـﺮوه Sham donor B
ﺗﻮﺳﻂ Tail cuffﻣﺘﺼﻞ ﺑﻪ دﺳﺘﮕﺎه Power labﻣﺎﻧﻴﺘﻮر و ﺛﺒﺖ ﮔﺮدﻳﺪ.
A
ﺑﺮرﺳﻲ ﺑﺎﻓﺖﺷﻨﺎﺳﻲ ﻛﻠﻴﻪﻫﺎ :ﻛﻠﻴﻪﻫﺎ در ﻓﺮﻣﺎﻟﻴﻦ %10ﻓﻴﻜﺲ و ﭘﺲ از آبﮔﻴﺮي در ﭘﺎراﻓﻴﻦ ﻗﺎﻟﺐﮔﻴﺮي ﮔﺮدﻳﺪﻧـﺪ .از اﻳـﻦ ﻛﻠﻴـﻪﻫـﺎ ﻣﻘـﺎﻃﻊ ﺑﺎﻓﺘﻲ )ﭼﻬﺎر ﻣﻴﻜﺮوﻣﺘﺮ( ﺗﻬﻴﻪ و ﺑﺎ اﺋﻮزﻳﻦ و ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ رﻧـﮓآﻣﻴـﺰي ﺷﺪ .ﺑﺮرﺳﻲ ﻣﻘﺎﻃﻊ ﺑﺎﻓﺘﻲ ﺑﺎ ﻣﻴﻜﺮوﺳﻜﻮپ ﻧـﻮري اﻧﺠـﺎم ﮔﺮدﻳـﺪ .ﻫﻤـﻪ ﻣﻘﺎﻃﻊ ﻛﻠﻴﻪ ﺣﺪاﻗﻞ در 10ﺣﻮزه ﺗﺼﺎدﻓﻲ ﻛﻪ ﺑﺎ ﻫﻢ ﺗﺪاﺧﻞ ﻧﺪاﺷـﺘﻨﺪ ﺑـﺎ D
ﺑﺰرگﻧﻤﺎﻳﻲ 400ﻣﺸﺎﻫﺪه ﺷﺪﻧﺪ .ﻣﻴﺰان آﺳـﻴﺐ ﺑـﻪ ﺻـﻮرت واﻛﻮﺋﻮﻟـﻪ
C
ﺷﺪن و اﻧﻬﺪام ﺳﻠﻮلﻫﺎ ،اﻧﻬﺪام ﺗﻮﺑﻮلﻫﺎ ،ﺣﻀﻮر Castﻫـﺎي ﻟﻮﻣﻴﻨـﺎل و ﻣﻮاد ﭘﺮوﺗﻴﻴﻨﻲ و از دﺳﺖ رﻓﺘﻦ ﻟﺒﻪ ﺑﺮوﺳﻲ ﺗﻮﺑﻮل ﭘﺮوﮔﺰﻳﻤﺎل ﻣﻲﺑﺎﺷﻨﺪ. در اﻳﻦ ﺗﺤﻘﻴﻖ ﻧﺘﺎﻳﺞ ﺑﺮاﺳﺎس ﺑﺮﻧﺎﻣﻪ آﻣﺎري SPSSوﻳﺮاﺳﺖ 10و ﺗﻮﺳﻂ Unpaired t- testاﻧﺠﺎم ﺷﺪ .دادهﻫﺎ ﺑﻪﺻـﻮرت Mean±S.E.Mﮔـﺰارش ﮔﺮدﻳﺪ و اﺧﺘﻼف ﻣﻌﻨﻲدار در ﺳﻄﺢ P<0/05در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪ.
ﺷﻜﻞ :1 -ﺗﻐﻴﻴﺮات ﻫﻴﺴﺘﻮﻟﻮژي ﻛﻠﻴﻪ در ﮔﺮوهﻫﺎي ﻣﺨﺘﻠﻒ .ﺑﺰرگﻧﻤﺎﻳﻲ:A .400 × : ﮔﺮوه :B ،IR donorﮔﺮوه :C ،Sham donorﮔﺮوه IR recipientو :Dﮔﺮوه .Sham recipient ﮔﺮوه IR donorدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorآﺳﻴﺐﻫﺎي ﺑﺴﻴﺎري را ﻧﺸﺎن داد .اﻳﻦ ﺗﻐﻴﻴﺮات
ﻳﺎﻓﺘﻪﻫﺎ
ﺷﺎﻣﻞ اﻧﻬﺪام ﮔﺴﺘﺮده ﺗﻮﺑﻮلﻫﺎ ،ﻧﻜﺮوز ﻧﺴﺒﺘﺎ وﺳﻴﻊ ﺑﻪﺧﺼﻮص در ﺗﻮﺑﻮلﻫﺎي ﭘﺮوﮔﺰﻳﻤﺎل ،وﺟﻮد اﻧﺴﺪاد ﺗﻮﺑﻮﻟﻲ ﻗﺎﺑﻞ ﻣﻼﺣﻈﻪ ﺑﻪوﻳﮋه در ﺗﻮﺑﻮلﻫﺎي اﻧﺘﻬﺎﻳﻲﺗﺮ ،ﻛﻢ ﺷﺪن ﺿﺨﺎﻣﺖ ﺳﻠﻮلﻫﺎ و ﺗﺤﺖ
ﺑﺮرﺳﻲ ﺗﻐﻴﻴﺮات ﻓﺸﺎر ﺳﻴﺴﺘﻮﻟﻴﻚ در ﮔﺮوهﻫﺎ :ﺗﻔـﺎوت ﻣﻌﻨـﻲداري ﺑﻴﻦ ﻣﻴﺎﻧﮕﻴﻦ ﻓﺸﺎر ﺳﻴﺴﺘﻮﻟﻴﻚ در ﮔﺮوهﻫﺎ ﻣﺸﺎﻫﺪه ﻧﮕﺮدﻳﺪ. ﺑﺮرﺳﻲ ﺗﻐﻴﻴﺮات ﺷﺎﺧﺺﻫﺎي ﻋﻤﻠﻜﺮدي ﻛﻠﻴﻪ در ﮔﺮوهﻫـﺎ :ﻏﻠﻈـﺖ
ﻓﺸﺎر ﺑﻮدن ﺳﻠﻮلﻫﺎي اﭘﻴﺘﻠﻴﺎل ﺗﻮﺑﻮﻟﻲ ﻣﻲﺑﺎﺷﺪ .در ﮔﺮوه ،Sham recipientاﮔﺮﭼﻪ ﻣﻘﺪاري از ﺿﺨﺎﻣﺖ ﺳﻠﻮلﻫﺎ ﻛﻢ ﺷﺪه و ﺗﺎ ﺣﺪي ﺣﺎﺷﻴﻪﻫﺎي ﻟﻮﻣﻴﻨﺎل ﺳﻠﻮلﻫﺎ Attenuationﻧﺸﺎن ﻣﻲدﻫﻨﺪ وﻟﻲ اﻧﻬﺪام ﺳﻠﻮلﻫﺎ و آﺳﻴﺐ ﻏﻴﺮ ﻗﺎﺑﻞ ﺑﺮﮔﺸﺘﻲ وﺟﻮد ﻧﺪارد .در ﮔﺮوه ،IR recipientﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺷﻢ ﻣﺮﺑﻮﻃﻪ واﻛﻮﺋﻮﻟﻪ ﺷﺪن ﺳﻠﻮلﻫﺎ و ﺗﺸﻜﻴﻞ ﻣﻘﺎدﻳﺮي رﺳﻮب درون ﺗﻮﺑﻮلﻫﺎ ﺑﻪ ﭼﺸﻢ ﻣﻲرﺳﺪ اﻣﺎ ﺗﻮﺑﻮلﻫﺎ ﻫﻨﻮز دﺳﺖ ﻧﺨﻮرده ﻫﺴﺘﻨﺪ و ﺗﻐﻴﻴﺮ ﻏﻴﺮ ﻗﺎﺑﻞ ﺑﺮﮔﺸﺘﻲ از ﺟﻤﻠﻪ ﻧﻜﺮوز ﺗﻮﺑﻮﻟﻲ
BUNدر ﭘﻼﺳﻤﺎي ﮔﺮوه IR donorاﻓﺰاﻳﺶ ﻣﻌﻨـﻲداري در ﻣﻘﺎﻳـﺴﻪ ﺑـﺎ
دﻳﺪه ﻧﻤﻲﺷﻮد .در ﻣﺠﻤﻮع اﻳﻦ ﮔﺮوه در آﻏﺎز ﮔﺴﺘﺮش آﺳﻴﺐ ﺑﺎﻓﺘﻲ اﺳﺖ و ﺗﻔﺎوت ﺑﺴﻴﺎري ﺑﺎ
ﮔﺮوه Sham donorداﺷﺖ )ﻧﻤﻮدار .(1aﺑﻪ اﻳﻦ ﺗﺮﺗﻴﺐ در اﻳﻦ ﺗﺤﻘﻴـﻖ
ﮔﺮوه IR donorدارد.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
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ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ و ﻫﻤﻜﺎران
اﻛﺴﻴﺪاﺗﻴﻮ در ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﭘﺲ از اﻟﻘﺎي ﻧﺎرﺳـﺎﻳﻲ ﺣـﺎد ﻛﻠﻴـﻪ اﻳـﺴﻜﻤﻴﻚ
ﻣﻌﻨﻲداري در ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorداﺷـﺖ )ﻧﻤـﻮدار .(3aﺑـﻪ
اﻓﺰاﻳﺶ ﻳﺎﻓﺖ .ﻫﻢﭼﻨﻴﻦ ﺗﻔﺎوت ﻣﻌﻨﻲداري در ﻣﻴﺰان MDAﺑﺎﻓـﺖ ﻛﻠﻴـﻪ
اﻳﻦ ﺗﺮﺗﻴﺐ در اﻳﻦ ﺗﺤﻘﻴﻖ ﻛﺎﻫﺶ ﻣﻴـﺰان ﮔﻠﻮﺗـﺎﺗﻴﻮن ﺑـﻪ ﻋﻨـﻮان اﻳﺠـﺎد
در ﮔﺮوهﻫﺎي IR recipientو Sham recipientدﻳﺪه ﺷﺪ )ﻧﻤـﻮدار .(2b
اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ در ﺑﺎﻓﺖ ﻛﻠﻴـﻪ ﭘـﺲ از اﻟﻘـﺎي ﻧﺎرﺳـﺎﻳﻲ ﺣـﺎد ﻛﻠﻴـﻪ
IR
اﻳــﺴﻜﻤﻴﻚ ﺗﻠﻘــﻲ ﮔﺮدﻳــﺪ .ﻫــﻢﭼﻨــﻴﻦ ﺗﻔــﺎوت ﻣﻌﻨــﻲداري در ﻣﻴــﺰان
recipientﺳﺒﺐ اﻓـﺰاﻳﺶ ﻣﻴـﺰان MDAدر اﻳـﻦ ﮔـﺮوه ﮔﺮدﻳـﺪ .ﻣﻴـﺰان
ﮔﻠﻮﺗﺎﺗﻴﻮن ﺑﺎﻓﺖ ﻛﻠﻴـﻪ در ﮔـﺮوهﻫـﺎي
IR recipientو Sham recipient
ﮔﻠﻮﺗﺎﺗﻴﻮن ) (Total glutathioneدر ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﮔﺮوه IR donorﻛـﺎﻫﺶ
دﻳـﺪه ﺷﺪ )ﻧﻤﻮدار .(3bﺑﻪ اﻳـﻦ ﺗﺮﺗﻴـﺐ اﻧﺘـﻘﺎل ﻟـﻜﻮﺳﻴـﺖﻫﺎي ﮔـﺮوه
ﺑﻪ اﻳﻦ ﺗﺮﺗﻴـﺐ اﻧﺘﻘـﺎل ﻟﻜﻮﺳـﻴﺖﻫـﺎي ﮔـﺮوه IR donorﺑـﻪ ﮔـﺮوه
ﻧﻤﻮدار :1 -ﺗﻐﻴﻴﺮات ﻏﻠﻈﺖ BUNو ﻛﺮاﺗﻴﻨﻴﻦ ﭘﻼﺳﻤﺎ در ﮔﺮوهﻫﺎي ﻣﺨﺘﻠﻒ (a .ﻣﻘﺎﻳﺴﻪ IR donorو (b .Sham donorﻣﻘﺎﻳﺴﻪ IR recipientو .Sham recipientﺳﺘﻮنﻫﺎ ﻧﻤﺎﻳﺎنﮔﺮ
ﻣﻴـﺎﻧﮕﻴﻦ±
ﺧﻄﺎي ﻣﻌﻴﺎر ﻣﻲﺑﺎﺷﺪ * .اﺧﺘﻼف ﻣﻌﻨﻲدار را ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه Sham donorدر ﺳﻄﺢ P<0/05ﻧﺸﺎن ﻣﻲدﻫﺪ.
ﻧﻤﻮدار :2 -ﺗﻐﻴﻴﺮات ﻏﻠﻈﺖ MDAﻛﻠﻴﻮي در ﮔﺮوهﻫﺎي ﻣﺨﺘﻠﻒ (a .ﻣﻘﺎﻳﺴﻪ IR donorو (b .Sham donorﻣﻘﺎﻳﺴﻪ IR recipientو .Sham recipientﺳﺘﻮنﻫﺎ ﻧﻤﺎﻳﺎنﮔﺮ ﻣﻴﺎﻧﮕﻴﻦ ±ﺧﻄﺎي ﻣﻌﻴـﺎر ﻣﻲﺑﺎﺷﺪ * .اﺧﺘﻼف ﻣﻌﻨﻲدار را ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه Shamﻣﺮﺑﻮﻃﻪ در ﺳﻄﺢ P<0/05ﻧﺸﺎن ﻣﻲدﻫﺪ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘﺲ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ از ﻣﻮش ﺑﺎ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﻛﻠﻴﻮي
73
ﻧﻤﻮدار :3 -ﺗﻐﻴﻴﺮات ﻏﻠﻈﺖ ﮔﻠﻮﺗﺎﺗﻴﻮن و FRAPﻛﻠﻴﻮي در ﮔﺮوهﻫﺎي ﻣﺨﺘﻠـﻒ (a .ﻣﻘﺎﻳـﺴﻪ IR donorو (b .Sham donorﻣﻘﺎﻳـﺴﻪ IR recipientو .Sham recipientﺳـﺘﻮنﻫـﺎ ﻧﻤﺎﻳـﺎنﮔـﺮ ﻣﻴﺎﻧﮕﻴﻦ ±ﺧﻄﺎي ﻣﻌﻴﺎر ﻣﻲﺑﺎﺷﺪ * .اﺧﺘﻼف ﻣﻌﻨﻲدار را ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه Shamﻣﺮﺑﻮﻃﻪ در ﺳﻄﺢ P<0/05ﻧﺸﺎن ﻣﻲدﻫﺪ.
ﻧﻤﻮدار :4 -ﺗﻐﻴﻴﺮات ﻣﻴﺰان آﻧﺰﻳﻢﻫﺎي ﺳﻮﭘﺮ اﻛﺴﻴﺪ دﻳﺴﻤﻮﺗﺎز و ﻛﺎﺗﺎﻻز ﻛﻠﻴـﻮي در ﮔـﺮوهﻫـﺎي ﻣﺨﺘﻠـﻒ (a .ﻣﻘﺎﻳـﺴﻪ IR donorو (b .Sham donorﻣﻘﺎﻳـﺴﻪ IR recipientو
Sham
.recipientﺳﺘﻮنﻫﺎ ﻧﻤﺎﻳﺎنﮔﺮ ﻣﻴﺎﻧﮕﻴﻦ ±ﺧﻄﺎي ﻣﻌﻴﺎر ﻣﻲﺑﺎﺷﺪ * .اﺧﺘﻼف ﻣﻌﻨﻲدار را ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه Shamﻣﺮﺑﻮﻃﻪ در ﺳﻄﺢ P<0/05ﻧﺸﺎن ﻣﻲدﻫﺪ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻬﺮي ﻛﺪﺧﺪاﻳﻲ و ﻫﻤﻜﺎران
74
IR donorﺑﻪ ﮔﺮوه IR recipientﺳﺒﺐ ﻛﺎﻫﺶ ﻣﻴﺰان ﮔﻠﻮﺗﺎﺗﻴﻮن ﺗـﺎم در
ﻣﻼﺣﻈﻪ ﺑﻪوﻳﮋه در ﺗﻮﺑﻮلﻫﺎي اﻧﺘﻬﺎﻳﻲﺗﺮ ،ﻛﻢ ﺷﺪن ﺿﺨﺎﻣﺖ ﺳﻠﻮلﻫﺎ و
اﻳﻦ ﮔﺮوه ﮔﺮدﻳﺪ .ﻣﻴﺰان ﻗﺪرت ﺗﺎم آﻧﺘـﻲ اﻛـﺴﻴﺪاﻧﻲ ) (FRAPدر ﺑﺎﻓـﺖ
Sham
ﻛﻠﻴﻪ ﮔﺮوه IR donorﻛـﺎﻫﺶ ﻣﻌﻨـﻲداري در ﻣﻘﺎﻳـﺴﻪ ﺑـﺎ ﮔـﺮوه
ﺗﺤﺖ ﻓﺸﺎر ﺑﻮدن ﺳﻠﻮلﻫﺎي اﭘﻴﺘﻠﻴﺎل ﺗﻮﺑﻮﻟﻲ ﻣﻲﺑﺎﺷﺪ .در ﮔـﺮوه
Sham
،recipientاﮔﺮﭼﻪ ﻣﻘﺪاري از ﺿﺨﺎﻣﺖ ﺳﻠﻮلﻫﺎ ﻛﻢ ﺷـﺪه و ﺗـﺎ ﺣـﺪي
donorداﺷﺖ )ﻧﻤﻮدار .(3aﺑﻪ اﻳﻦ ﺗﺮﺗﻴﺐ در اﻳﻦ ﺗﺤﻘﻴﻖ ﻛﺎﻫﺶ ﻣﻴـﺰان
ﺣﺎﺷﻴﻪﻫﺎي ﻟﻮﻣﻴﻨﺎل ﺳﻠﻮلﻫﺎ ﻛﺎﻫﺶ ﻧﺸﺎن ﻣﻲدﻫﻨﺪ وﻟﻲ اﻧﻬﺪام ﺳﻠﻮلﻫـﺎ
FRAPﺑﻪ ﻋﻨﻮان اﻳﺠﺎد اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ در ﺑﺎﻓﺖ ﻛﻠﻴـﻪ ﭘـﺲ از اﻟﻘـﺎي
و آﺳﻴﺐ ﻏﻴﺮ ﻗﺎﺑﻞ ﺑﺮﮔـﺸﺘﻲ وﺟـﻮد ﻧـﺪارد )ﺷـﻜﻞ .(1Dدر ﮔـﺮوه
IR
ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴﻪ اﻳﺴﻜﻤﻴﻚ ﺗﻠﻘﻲ ﮔﺮدﻳﺪ .اﮔﺮﭼﻪ اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫـﺎي
،recipientﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺷـﻢ ﻣﺮﺑﻮﻃـﻪ واﻛﻮﺋﻮﻟـﻪ ﺷـﺪن ﺳـﻠﻮلﻫـﺎ و
ﮔﺮوه IR donorﺑﻪ ﮔـﺮوه IR recipientﺳـﺒﺐ ﻛـﺎﻫﺶ ﻣﻴـﺰان ﻓﻌﺎﻟﻴـﺖ
ﺗﺸﻜﻴﻞ ﻣﻘﺎدﻳﺮي رﺳﻮب درون ﺗﻮﺑﻮلﻫﺎ ﺑﻪ ﭼﺸﻢ ﻣﻲرﺳﺪ اﻣﺎ ﺗﻮﺑﻮلﻫـﺎ
FRAPدر اﻳﻦ ﮔﺮوه ﮔﺮدﻳﺪ ،اﻣﺎ از ﻧﻈﺮ آﻣـﺎري اﻳـﻦ ﺗﻔـﺎوت در ﻣﻴـﺰان
ﻫﻨﻮز دﺳﺖ ﻧﺨﻮرده ﻫﺴﺘﻨﺪ و ﺗﻐﻴﻴﺮ وﺳﻴﻊ ﻏﻴﺮ ﻗﺎﺑﻞ ﺑﺮﮔـﺸﺘﻲ از ﺟﻤﻠـﻪ
Sham recipient
ﻧﻜﺮوز ﻛﺎﻣﻞ ﺗﻮﺑﻮﻟﻲ دﻳﺪه ﻧﻤﻲﺷﻮد )ﺷﻜﻞ .(1Cدر ﻣﺠﻤﻮع اﻳﻦ ﮔـﺮوه
)(SOD
در آﻏﺎز ﮔﺴﺘﺮش آﺳﻴﺐ ﺑﺎﻓﺘﻲ اﺳﺖ و اﮔﺮﭼـﻪ ﺑـﺎ ﮔـﺮوه ﺷـﻢ ﻣﺮﺑﻮﻃـﻪ
FRAPﺑﺎﻓــﺖ ﻛﻠﻴــﻪ در ﮔــﺮوهﻫــﺎي IR recipientو
ﻣﻌﻨﻲدار ﻧﺒﻮد )ﻧﻤﻮدار .(3bﻣﻴﺰان آﻧﺰﻳﻢ ﺳﻮﭘﺮ اﻛﺴﻴﺪ دﻳـﺴﻤﻮﺗﺎز
در ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﮔﺮوه IR donorﻛﺎﻫﺶ ﻣﻌﻨﻲداري در ﻣﻘﺎﻳـﺴﻪ ﺑـﺎ ﮔـﺮوه
ﺑﺴﻴﺎر ﻣﺘﻔﺎوت اﺳﺖ وﻟﻲ ﺑﺎ ﮔﺮوه IR donorﻫﻢ ﺗﻔﺎوت ﺑﺴﻴﺎري دارد.
Sham donorداﺷﺖ )ﻧﻤﻮدار .(4aﺑﻪ اﻳﻦ ﺗﺮﺗﻴﺐ در اﻳﻦ ﺗﺤﻘﻴﻖ ﻛﺎﻫﺶ ﻣﻴﺰان SODﺑﻪ ﻋﻨﻮان اﻳﺠﺎد اﺳﺘﺮس اﻛـﺴﻴﺪاﺗﻴﻮ در ﺑﺎﻓـﺖ ﻛﻠﻴـﻪ ﭘـﺲ از
ﺑﺤﺚ
اﻟﻘﺎي ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴﻪ اﻳﺴﻜﻤﻴﻚ ﺗﻠﻘـﻲ ﮔﺮدﻳـﺪ .ﻫـﻢ ﭼﻨـﻴﻦ ﺗﻔـﺎوت ﻣﻌﻨﻲداري در ﻣﻴﺰان SODﺑﺎﻓـﺖ ﻛﻠﻴـﻪ در ﮔـﺮوهﻫـﺎي IR recipientو
ﺗﺎﻛﻨﻮن ﻣﻄﺎﻟﻌﺎت زﻳﺎدي درﺑـﺎره ﻋﻮاﻣـﻞ دﺧﻴـﻞ در اﻳﺠـﺎد آﺳـﻴﺐ
Sham recipientدﻳــﺪه ﺷــﺪ )ﻧﻤــﻮدار .(4bﺑــﻪ اﻳــﻦ ﺗﺮﺗﻴــﺐ اﻧﺘﻘــﺎل
اﻳﺴﻜﻤﻲ ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد در اﻧﺪامﻫﺎي ﻣﺨﺘﻠﻒ ﺻﻮرت ﮔﺮﻓﺘﻪ اﺳـﺖ
ﻟﻜﻮﺳﻴﺖﻫﺎي ﮔـﺮوه IR donorﺑـﻪ ﮔـﺮوه IR recipientﺳـﺒﺐ ﻛـﺎﻫﺶ
ﻛــﻪ ﺑﺮﺧــﻲ از آنﻫــﺎ ﻣﻜﺎﻧﻴــﺴﻢﻫــﺎي اﻟﺘﻬــﺎﺑﻲ از ﻗﺒﻴــﻞ اﻧﻔﻴﻠﺘﺮاﺳــﻴﻮن
(Catalase
ﻟﻜﻮﺳﻴﺖﻫﺎ ،اﻟﻘﺎي ﺳﺎﻳﺘﻮﻛﻴﻦﻫﺎ و ﻛﻤﻮﻛﻴﻦﻫﺎ را ﺑـﻪ ﻋﻨـﻮان ﻓﺎﻛﺘﻮرﻫـﺎي
) activityدر ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﮔﺮوه IR donorﻛﺎﻫﺶ ﻣﻌﻨﻲداري در ﻣﻘﺎﻳـﺴﻪ
ﻣﻮﺛﺮ ﭘﻴﺸﻨﻬﺎد ﻧﻤﻮدهاﻧﺪ .از اﻳﻦرو ﺑﺴﻴﺎري ﺗﺤﻘﻴﻘـﺎت ﺑـﻪ ﺑﺮرﺳـﻲ ﻧﻘـﺶ
ﻣﻴﺰان SODدر اﻳﻦ ﮔﺮوه ﮔﺮدﻳﺪ .ﻣﻴﺰان ﻓﻌﺎﻟﻴﺖ آﻧﺰﻳﻢ ﻛﺎﺗﺎﻻز
10-12
ﺑﺎ ﮔﺮوه Sham donorداﺷـﺖ )ﻧﻤـﻮدار .(4aﺑـﻪ اﻳـﻦ ﺗﺮﺗﻴـﺐ در اﻳـﻦ
ﻟﻜﻮﺳﻴﺖﻫـﺎ در اﻳﺠـﺎد اﻳـﻦ آﺳـﻴﺐ ﭘﺮداﺧﺘـﻪ اﺳـﺖ.
ﺗﺤﻘﻴﻖ ﻛﺎﻫﺶ ﻣﻴﺰان ﻛﺎﺗﺎﻻز ﺑﻪ ﻋﻨﻮان اﻳﺠﺎد اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ در ﺑﺎﻓﺖ
ﻣﻄﺎﻟﻌﺎت ،روي ﺑﺮرﺳﻲ ﻧﻘﺶ ﻟﻜﻮﺳﻴﺖﻫـﺎ در ﻳـﻚ ﻋـﻀﻮ ﻣﺘﻌﺎﻗـﺐ
ﻛﻠﻴﻪ ﭘﺲ از اﻟﻘﺎي ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴﻪ اﻳﺴﻜﻤﻴﻚ ﺗﻠﻘـﻲ ﮔﺮدﻳـﺪ .اﮔﺮﭼـﻪ
ﻫﻤﺎن ﻋﻀﻮ ﺻﻮرت ﮔﺮﻓﺘﻪ اﺳﺖ ﻛﻪ ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺣﻀﻮر و دﺧﺎﻟﺖ ﺳﺎﻳﺮ
اﻧﺘﻘﺎل ﻟﻜﻮﺳـﻴﺖﻫـﺎي ﮔـﺮوه IR donorﺑـﻪ ﮔـﺮوه IR recipientﺳـﺒﺐ
ﻋﻮاﻣﻞ ﻧﺘﺎﻳﺞ ﻣﺘﻔﺎوﺗﻲ داﺷﺘﻪ اﺳﺖ .ﺑﻪ ﻋﻨﻮان ﻣﺜﺎل ﻣﻄﺎﻟﻌﺎت اﺧﻴـﺮ ﻧـﺸﺎن
ﻛﺎﻫﺶ ﻣﻴﺰان ﻓﻌﺎﻟﻴﺖ ﻛﺎﺗﺎﻻز در اﻳﻦ ﮔﺮوه ﮔﺮدﻳﺪ ،اﻣﺎ از ﻧﻈﺮ آﻣﺎري اﻳﻦ
دادهاﻧﺪ ﻛﻪ IRﻛﻠﻴـﻮي ﻣﻮﺟـﺐ اﻓـﺰاﻳﺶ ﺑﻴـﺎن TNF-αو اﻓـﺰاﻳﺶ ورود
ﺗﻔﺎوت در ﻣﻴﺰان ﻛﺎﺗﺎﻻز ﺑﺎﻓﺖ ﻛﻠﻴﻪ در ﮔﺮوهﻫﺎي IR recipientو
Sham
recipientﻣﻌﻨﻲدار ﻧﺒﻮد )ﻧﻤﻮدار .(4b
14و13
ﻧﻮﺗﺮوﻓﻴﻞﻫﺎ ﺑﻪداﺧﻞ ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﻣﻲﺷﻮد.
اﻏﻠـﺐ اﻳـﻦ
در ﺳﺎل ،2000
IR
Mizutani
ﺑﺎ اﺳﺘﻔﺎده از ﭘﺮوﺗﻴﻴﻦ Cﻓﻌﺎل ﺷﺪه از ﻓﻌﺎل ﺷﺪن ﻟﻜﻮﺳﻴﺖﻫﺎ ﺟﻠﻮﮔﻴﺮي
ﺑﺮرﺳﻲ ﺗﻐﻴﻴﺮات ﺑﺎﻓﺖﺷﻨﺎﺳﻲ ﻛﻠﻴﻪ در ﮔﺮوهﻫﺎ :ﺑﺎﻓﺖ ﻛﻠﻴﻪ در ﮔﺮوه
4
ﻛﺮده و در ﻧﺘﻴﺠﻪ از اﻳﺠﺎد آﺳﻴﺐ ﺑﺮ اﺛـﺮ IRﻛﻠﻴـﻮي ﺟﻠـﻮﮔﻴﺮي ﻧﻤـﻮد.
Sham donorﺿﺎﻳﻌﻪ ﻗﺎﺑﻞ ﻣﻼﺣﻈﻪاي را ﺑﺎ ﻣﻴﻜﺮوﺳﻜﻮپ ﻧـﻮري ﻧـﺸﺎن
وي ﻫﻢﭼﻨﻴﻦ در ﺳـﺎل 2003در ﻣﻄﺎﻟﻌـﻪ دﻳﮕـﺮي ﮔـﺰارش ﻧﻤـﻮد ﻛـﻪ
ﻧﻤﻲدﻫﺪ )ﺷﻜﻞ .(1Bﺑﺎﻓﺖﻫﺎ در ﮔﺮوه IR donorدر ﻣﻘﺎﻳﺴﻪ ﺑـﺎ ﮔـﺮوه
آﻧﺘﻲﺗﺮوﻣﺒﻴﻦ ﻧﻴﺰ ﺑﺎ ﻣﻬﺎر ﻓﻌﺎل ﺷﺪن ﻟﻜﻮﺳﻴﺖﻫـﺎ IRﻛﻠﻴـﻮي را ﻛـﺎﻫﺶ 15
Sham donorآﺳﻴﺐﻫﺎي ﺑـﺴﻴﺎري را ﻧـﺸﺎن داد )ﺷـﻜﻞ .(1Aدر اﻳـﻦ
ﻣﻲدﻫﺪ.
ﮔﺮوه ،ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻃﻮﻻﻧﻲ ﺑﻮدن زﻣـﺎن ﭘﺮﻓﻴـﻮژن ﻣﺠـﺪد )ﺳـﻪ ﺳـﺎﻋﺖ(
ﻟﻨﻔﻮﺳﻴﺖ CD4/CD8درﻳﺎﻓﺖ ﻛﻪ اﻳﻦ ﻣﻮشﻫـﺎ ﻧـﺴﺒﺖ ﺑـﻪ ﻣـﻮشﻫـﺎي
ﺑﺎﻓﺖ ﻛﻠﻴﻪ ﺗﻐﻴﻴﺮات ﻗﺎﺑﻞ ﻣﻼﺣﻈﻪاي را ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه Shamﻧﺸﺎن داد.
ﻧﺮﻣﺎل ،در ﺑﺮاﺑﺮ IRﻛﻠﻴﻮي دﭼﺎر آﺳﻴﺐ ﻛﻢﺗﺮي ﻣـﻲﺷـﻮﻧﺪ 16.از ﺳـﻮي
اﻳﻦ ﺗﻐﻴﻴﺮات ﺷﺎﻣﻞ اﻧﻬـﺪام ﮔـﺴﺘﺮده ﺗﻮﺑـﻮل ﻫـﺎ ،ﻧﻜـﺮوز ﻧـﺴﺒﺘﺎ وﺳـﻴﻊ
دﻳﮕﺮ Park ،ﻣﻄﺮح ﻧﻤﻮد ﻛﻪ ﺿﺎﻳﻌﺎت ﻛﻠﻴـﻮي ﻣﺘﻌﺎﻗـﺐ IRارﺗﺒـﺎﻃﻲ ﺑـﺎ
ﺑﻪ ﺧﺼﻮص در ﺗﻮﺑﻮلﻫﺎي ﭘﺮوﮔﺰﻳﻤـﺎل ،وﺟـﻮد اﻧـﺴﺪاد ﺗﻮﺑـﻮﻟﻲ ﻗﺎﺑـﻞ
اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻮﻟﻴﻦﻫﺎ و ﻳﺎ ﻟﻨﻔﻮﺳـﻴﺖﻫـﺎي Tﻧـﺪارد 17.ﻫـﻢﭼﻨـﻴﻦ ﻛـﺎﻫﺶ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
Rabbﻧﻴﺰ در ﻣﻄﺎﻟﻌـﻪ ﺧـﻮد ﺑـﺮ روي ﻣـﻮشﻫـﺎي ﻓﺎﻗـﺪ ژن
آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘﺲ از اﻧﺘﻘﺎل ﻟﻜﻮﺳﻴﺖﻫﺎ از ﻣﻮش ﺑﺎ اﻳﺴﻜﻤﻲ -ﺧﻮنرﺳﺎﻧﻲ ﻣﺠﺪد ﻛﻠﻴﻮي
75
ﻧﻮﺗﺮوﻓﻴﻞﻫﺎ در ﻣﻮشﻫﺎي ﻓﺎﻗﺪ ژن ﻓﻌﺎلﻛﻨﻨﺪه Recombinaseﻧﺘﻮاﻧـﺴﺖ
ﻣﺸﺎﺑﻪ ﻳﻌﻨﻲ ﻛﻠﻴﻪﻫﺎي ﭘﺬﻳﺮﻧـﺪه ﺑﺮرﺳـﻲ ﻧﻤـﺎﻳﻴﻢ .وﻳﮋﮔـﻲ اﻳـﻦ ﺗﺤﻘﻴـﻖ
B
ﺑﺮرﺳﻲ ﺗﻐﻴﻴﺮات ﻛﻠﻴﻮي در ﻛﻠﻴﻪاي اﺳﺖ ﻛﻪ ﺧﻮد ﻣﺴﺘﻘﻴﻤﺎ ﺗﺤﺖ اﻟﻘـﺎي
ﻳﺎ Tﺑﻪ اﻳﻦ ﻣﻮشﻫﺎ ﺗﻮاﻧﺴﺖ ﻣﺤﺎﻓﻈﺖ ﭼﺸﻤﮕﻴﺮي ﻧﺸﺎن دﻫﺪ .ﻫﻢﭼﻨﻴﻦ
IRﻗﺮار ﻧﮕﺮﻓﺘﻪ اﺳﺖ .ﺑﻨﺎﺑﺮاﻳﻦ اﺛﺮات ﻧﺎﺷﻲ از IRﻋﻀﻮ ﺣـﺬف ﺷـﺪه و
در ﻣﻘﺎﺑﻞ آﺳﻴﺐﻫﺎي ﻛﻠﻴﻮي ﻣﺤﺎﻓﻈﺖ ﻧﻤﺎﻳﺪ 18،ﺑﻠﻜﻪ اﻧﺘﻘﺎل ﺳﻠﻮلﻫﺎي
اﻓﺰودن ﻟﻜﻮﺳﻴﺖﻫﺎ ﺑﻪ ﻣﺤﻴﻂ ﺣﺎوي ﺳﻠﻮلﻫﺎي ﻣﻐﺰي اﻧﺴﺎﻧﻲ ﺿـﺎﻳﻌﺎت
ﺗﻨﻬﺎ اﺛﺮ ﻟﻜﻮﺳﻴﺖﻫﺎي ﻓﻌﺎل ﺷـﺪه را ﺑﺮرﺳـﻲ ﻣـﻲﻧﻤﺎﻳـﺪ .ﻟـﺬا ﺗﻐﻴﻴـﺮات
19
ﺣﺎﺻﻞ ﻣﻲﺗﻮاﻧﺪ ﻣﻄﺮح ﻛﻨﻨﺪه ﺗﻐﻴﻴﺮات اﻳﺠﺎد ﺷﺪه در ﻛﻠﻴﻪ ﺳﺎﻟﻢ ﻣﻮﺟﻮد
IL-10
در ﺑﺪن ﻣﺘﻌﺎﻗﺐ IRﻛﻠﻴﻪ دﻳﮕﺮ ﻫﻢ ﺑﺎﺷﺪ .ﻣﻮشﻫﺎ در دو ﮔـﺮوه Shamو
آﺳﻴﺐﻫﺎي IRﻛﻠﻴﻮي را ﻛﻢ ﻛﻨﺪ 20.ﻟﺬا اﻳـﻦ ﻣﺠﻤﻮﻋـﻪ ﻣﻄﺎﻟﻌـﺎت ﻧـﺸﺎن
IRﻛﻠﻴــﻮي دوﻃﺮﻓــﻪ ﻛــﻪ 60دﻗﻴﻘــﻪ اﻧــﺴﺪاد دو ﻃﺮﻓــﻪ ﺷــﺮﻳﺎن ﻛﻠﻴــﻮي
IR
)اﻳﺴﻜﻤﻲ( و ﺑﻪدﻧﺒﺎل آن ﺳﻪ ﺳﺎﻋﺖ ﭘﺮﻓﻴﻮژن ﻣﺠـﺪد را ﺗﺤﻤـﻞ ﻛﺮدﻧـﺪ،
ﺑﺴﻴﺎر ﭘﻴﭽﻴﺪه ﻣﻲﺑﺎﺷﻨﺪ .ﻳﻜﻲ از ﻋﻮاﻣﻞ آﺳﻴﺐ رﺳﺎن ﻣﺘﻌﺎﻗﺐ IRﻛﻠﻴﻮي
ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﭘﺲ از آن ﺣﻴﻮاﻧﺎت ﺑﻴﻬﻮش ﺷﺪه و ﻧﻤﻮﻧﻪ ﺧـﻮن و ﺑﺎﻓـﺖ
اﻓﺰاﻳﺶ ﺗﻮﻟﻴﺪ ﻣﺘﺎﺑﻮﻟﻴﺖﻫﺎي ﻓﻌﺎل اﻛﺴﻴﮋن ) (ROSﺗﻮﺳـﻂ ﻓﺎﮔﻮﺳـﻴﺖﻫـﺎ
ﻛﻠﻴﻮي ﺟﻤﻊآوري ﮔﺮدﻳﺪ .ﻟﻜﻮﺳﻴﺖﻫﺎ از ﺧﻮن ﺟﺪا ﺷﺪه و ﺑﻪ دو ﮔﺮوه
ﻣﻲﺑﺎﺷﺪ Demirbilek .از ﻳﻚ آﻧﺘﻲاﻛـﺴﻴﺪان ﺑـﻪ ﻧـﺎم ﭘﻠـﻲانﻓـﺴﻔﺎﺗﻴﺪﻳﻞ
ﭘﺬﻳﺮﻧﺪه ﻣﻨﺘﻘﻞ ﺷﺪﻧﺪ :ﻣﻮشﻫﺎي ﭘﺬﻳﺮﻧﺪه ﻛﻪ ﻟﻜﻮﺳﻴﺖﻫﺎي ﮔﺮوه ﺷﻢ را
ﻛﻮﻟﻴﻦ ) (Polyenylphosphatidylcholineﺟﻬﺖ ﻛﺎﻫﺶ ﺿﺎﻳﻌﺎت ﻧﺎﺷﻲ
درﻳﺎﻓــﺖ ﻛﺮدﻧــﺪ ) (Sham recipientو ﻣــﻮشﻫــﺎي ﭘﺬﻳﺮﻧــﺪه ﻛــﻪ
از IRﻛﻠﻴﻮي اﺳﺘﻔﺎده ﻛﺮده و درﻳﺎﻓﺖ ﻛﻪ اﻳﻦ آﻧﺘﻲاﻛﺴﻴﺪان اﺛﺮ ﻣﺤﺎﻓﻈﺘﻲ
ﻟﻜﻮﺳﻴﺖﻫﺎي ﮔﺮوه IRرا درﻳﺎﻓﺖ ﻧﻤﻮدﻧـﺪ ) .(IR recipientﺑﻌـﺪ از 24
در IRﻛﻠﻴﻮي دارد 21.ﻫﻢﭼﻨﻴﻦ در ﺳﺎلﻫﺎي اﺧﻴﺮ ﻣﻄﺮح ﺷﺪه اﺳﺖ ﻛـﻪ
ﺳﺎﻋﺖ ﻣﻮشﻫﺎي ﭘﺬﻳﺮﻧﺪه ﺑﻴﻬﻮش ﺷﺪﻧﺪ و ﻧﻤﻮﻧﻪﻫـﺎي ﺧـﻮن و ﺑﺎﻓـﺖ
آﺳﻴﺐ ﻳﻚ ﻋﻀﻮ ﻣﻲﺗﻮاﻧﺪ ﺗﻮﺳﻂ ﻋﻮاﻣﻞ ﻣﺨﺘﻠﻒ در اﺧﺘﻼل اﻧـﺪامﻫـﺎي
Sham
ﺳﻠﻮﻟﻲ را در ﻳﻚ ﻣﺪل ﻣﺤﺮوﻣﻴﺖ از ﮔﻠـﻮﻛﺰ و اﻛـﺴﻴﮋن ﻛـﺎﻫﺶ داد. ﺳﻠﻮلﻫﺎي Bﺧﺎرج ﭘﺮﻳﺘﻮان ﺗﻮاﻧﺴﺖ اﺣﺘﻤﺎﻻ از ﻃﺮﻳـﻖ اﻓـﺰاﻳﺶ
ﻣﻲدﻫﺪ ﻛﻪ ﻣﻜﺎﻧﻴﺴﻢﻫﺎي در ﺑﺮﮔﻴﺮﻧﺪه ﻧﻘﺶ ﻟﻜﻮﺳﻴﺖﻫـﺎ در آﺳـﻴﺐ
دﻳﮕﺮ ﻧﻴﺰ ﻧﻘﺶ داﺷﺘﻪ ﺑﺎﺷﺪ Hassoun .در ﺑﺮرﺳﻲ ﺧﻮد ﻧﺸﺎن داد ﻛـﻪ
ﻛﻠﻴﻪ ﺟﻤﻊآوري ﺷﺪ .در ﮔـﺮوه IR recipientﻧـﺴﺒﺖ ﺑـﻪ ﮔـﺮوه
IR
recipientﻣﻴــﺰان MDAﺑﺎﻓــﺖ ﻛﻠﻴــﻪ ﺑ ـﻪﻃــﻮر ﻣﻌﻨــﻲداري اﻓــﺰاﻳﺶ و
ﻛﻠﻴﻮي ﻣﻮﺟﺐ آﺳـﻴﺐ ﺑﺎﻓـﺖ رﻳـﻪ ﺑـﻪ ﻋﻨـﻮان ﻳـﻚ ﻋـﻀﻮ دوردﺳـﺖ
ﮔﻠﻮﺗﺎﺗﻴﻮن ﺗﺎم و ﻣﻴﺰان ﻓﻌﺎﻟﻴﺖ آﻧﺰﻳﻢ SODﻛﻠﻴﻮي ﺑـﻪﻃـﻮر ﻣﻌﻨـﻲداري
) (Remoteﻣﻲﺷـﻮد IR .ﻛﻠﻴـﻮي ﻣﻮﺟـﺐ اﻓـﺰاﻳﺶ ﻧﻔﻮذﭘـﺬﻳﺮي رﻳـﻮي
ﻛﺎﻫﺶ ﻳﺎﻓﺘﻨﺪ .ﺷﺎﺧﺺﻫﺎي ﻋﻤﻠﻜﺮدي ﻛﻠﻴﻮي ﺷـﺎﻣﻞ BUNو ﻛـﺮاﺗﻴﻨﻴﻦ
ﮔﺮدﻳﺪ و در آزﻣﺎﻳﺸﺎت ﺑﺎﻓﺖﺷﻨﺎﺳـﻲ ﻧﻴـﺰ اﻟﺘﻬـﺎب ﺳـﻠﻮلﻫـﺎي رﻳـﻮي
ﭘﻼﺳﻤﺎ اﮔﺮﭼﻪ در ﮔﺮوه IRدﻫﻨﺪه ﺑﺎ ﺷﻢ ﺗﻔﺎوت ﻣﻌﻨﻲداري داﺷﺖ وﻟﻲ
ﻣﺸﺎﻫﺪه ﺷﺪ Liu 1.اﻟﺘﻬـﺎب و ﺗﻐﻴﻴـﺮات ﻋﻤﻠﻜـﺮدي ﺑﺎﻓـﺖ ﻣﻐـﺰ را ﻧﻴـﺰ
اﻳﻦ ﭘﺎراﻣﺘﺮﻫﺎ در دو ﮔﺮوه ﭘﺬﻳﺮﻧﺪه ﺑـﺎ ﻳﻜـﺪﻳﮕﺮ ﺗﻔـﺎوت ﻣﻌﻨـﻲداري را
ﺑﻪدﻧﺒﺎل IRﻛﻠﻴﻮي ﮔﺰارش ﻛﺮد 6.در ﺳﺎل 2009ﻧﻴﺰ ﮔـﺰارش ﺷـﺪه ﻛـﻪ
ﻧﺸﺎن ﻧﺪادﻧﺪ .در ﺑﺮرﺳﻲﻫﺎي ﻫﻴـﺴﺘﻮﻟﻮژﻳﻚ ﺑﺎﻓـﺖ ﻛﻠﻴـﻪ در ﮔـﺮوه
IR
ﺑﻪدﻧﺒﺎل IRﻛﻠﻴﻮي ﻏﻠﻈﺖ ﻛﺒﺪي ،TNF-αاﻳﻨﺘﺮﻟﻮﻛﻴﻦ MDA ،10اﻓﺰاﻳﺶ
donorدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه Sham donorآﺳﻴﺐﻫﺎي ﺑـﺴﻴﺎري را ﺷـﺎﻣﻞ
و ﻏﻠﻈﺖ ﮔﻠﻮﺗﺎﺗﻴﻮن اﺣﻴﺎ ﺷﺪه ﻛﺎﻫﺶ ﻳﺎﻓﺘﻪ و ﻣﻄﺎﻟﻌﺎت ﺑﺎﻓﺖﺷﻨﺎﺳﻲ ﻧﻴﺰ
اﻧﻬﺪام ﮔﺴﺘﺮده ﺗﻮﺑـﻮلﻫـﺎ ،ﻧﻜـﺮوز ﺑـﻪ ﻧـﺴﺒﺖ وﺳـﻴﻊ ﺑـﻪﺧـﺼﻮص در
آﺳﻴﺐ ﺑﺎﻓﺖ ﻛﺒﺪي را ﺗﺎﻳﻴﺪ ﻛﺮدهاﻧﺪ 8.ﺟﻬﺖ ﺑﺮرﺳﻲ ﻧﻘـﺶ اﺧﺘـﺼﺎﺻﻲ
ﺗﻮﺑﻮلﻫﺎي ﭘﺮوﮔﺰﻳﻤﺎل ،وﺟﻮد اﻧﺴﺪاد ﺗﻮﺑﻮﻟﻲ ﻗﺎﺑﻞ ﻣﻼﺣﻈﻪ ﺑـﻪوﻳـﮋه در
ﻟﻜﻮﺳﻴﺖﻫﺎ ،در ﻳﻚ ﻣﻄﺎﻟﻌﻪ اﺧﻴﺮ ﻣـﺎ ﻧﻘـﺶ اﻧﺘﻘـﺎل ﻟﻜﻮﺳـﻴﺖﻫـﺎ را در
ﺗﻮﺑﻮلﻫﺎي اﻧﺘﻬﺎﻳﻲﺗﺮ ،ﻛﻢ ﺷﺪن ﺿﺨﺎﻣﺖ ﺳﻠﻮلﻫﺎ و ﺗﺤﺖ ﻓـﺸﺎر ﺑـﻮدن
اﻟﻘﺎي آﺳﻴﺐ ﻛﺒﺪي ﺑﻪدﻧﺒﺎل اﻳﺴﻜﻤﻲ -ﭘﺮﻓﻴﻮژن ﻣﺠﺪد ﻛﻠﻴﻮي در ﻣـﻮش
ﺳﻠﻮلﻫﺎي اﭘﻴﺘﻠﻴﺎل ﺗﻮﺑﻮﻟﻲ ﻧﺸﺎن داد .در ﮔﺮوه ،IR recipientﻧﺴﺒﺖ ﺑـﻪ
ﺳﻮري Inbredﺑﺮرﺳﻲ ﻧﻤﻮده و ﻧﺸﺎن دادﻳﻢ ﻛـﻪ ﻟﻜﻮﺳـﻴﺖﻫـﺎي ﻓﻌـﺎل
ﮔﺮوه ﺷﻢ ﻣﺮﺑﻮﻃﻪ واﻛﻮﺋﻮﻟﻪ ﺷﺪن ﺳﻠﻮلﻫﺎ و ﺗﺸﻜﻴﻞ ﻣﻘـﺎدﻳﺮي رﺳـﻮب
ﺷﺪه در اﺛﺮ IRﻛﻠﻴﻮي ﻣﻲﺗﻮاﻧﻨﺪ در ﻛﺒﺪ ﻣﻮش ﭘﺬﻳﺮﻧﺪه اﻳﺠﺎد ﺿـﺎﻳﻌﺎت
درون ﺗﻮﺑﻮلﻫﺎ ﺑﻪ ﭼـﺸﻢ ﻣـﻲرﺳـﺪ .در ﻣﺠﻤـﻮع اﻳـﻦ ﮔـﺮوه در آﻏـﺎز
ﺑﺎﻓﺘﻲ و اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ ﻧﻤﻮده و آﻧﺰﻳﻢﻫﺎي ﻛﺒـﺪي را ﻧﻴـﺰ در ﺧـﻮن
ﮔﺴﺘﺮش آﺳﻴﺐ ﺑﺎﻓﺘﻲ اﺳـﺖ و اﮔﺮﭼـﻪ ﺑـﺎ ﮔـﺮوه ﺷـﻢ ﻣﺮﺑﻮﻃـﻪ ﺑـﺴﻴﺎر
اﻓﺰاﻳﺶ دﻫﻨﺪ 15.اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﻪ ﺧـﻮﺑﻲ ﻧـﺸﺎن داد ﻛـﻪ ﻟﻜﻮﺳـﻴﺖﻫـﺎ ﺑـﻪ
ﻣﺘﻔﺎوت اﺳﺖ وﻟﻲ ﺑﺎ ﮔـﺮوه IR donorﻫـﻢ ﺗﻔـﺎوت ﺑـﺴﻴﺎري دارد .در
ﺗﻨﻬﺎﻳﻲ و ﺑﺪون ﺣﻀﻮر ﺳﺎﻳﺮ ﻋﻮاﻣﻞ ﭘﻼﺳﻤﺎﻳﻲ و ﻳﺎ ﻣﻴﺎﻧﺠﻲﻫﺎي ﻋـﺼﺒﻲ
ﻣﻘﺎﻟﻪ ﻣﺸﺎﺑﻬﻲ Burne-Taneyﻧﺸﺎن داد ﻛﻪ اﻧﺘﻘﺎل ﻟﻨﻔﻮﺳﻴﺖﻫـﺎ از ﻣـﻮش
اﻧﺘﻘﺎل ﻳﺎﻓﺘﻪ از دﻫﻨﺪه ﻣﻲﺗﻮاﻧﻨﺪ در اﻳﺠﺎد ﺿﺎﻳﻌﺎت در ﻛﺒﺪ ﮔﻴﺮﻧﺪه ﻧﻘـﺶ
دﭼﺎر IRﻛﻠﻴﻮي ﻣﻲﺗﻮاﻧﺪ در ﮔﻴﺮﻧﺪه ﺳﺎﻟﻢ اﻳﺠـﺎد ﺿـﺎﻳﻌﻪ ﻛﻠﻴـﻮي و در 22
داﺷــﺘﻪ ﺑﺎﺷــﻨﺪ .در اداﻣــﻪ و در ﻃــﺮح ﺣﺎﺿــﺮ ﺑــﺮ آن ﺷــﺪﻳﻢ ﺗــﺎ ﻧﻘــﺶ
ﻧﺘﻴﺠﻪ آﻟﺒﻮﻣﻴﻨﻮري ﻧﻤﺎﻳﺪ .ﻫﻢﭼﻨﻴﻦ ﻣﻘﺎﻳﺴﻪ آﺳﻴﺐﭘﺬﻳﺮي ﻛﻠﻴﻪ ﺑـﺎ ﻛﺒـﺪ
ﻟﻜﻮﺳﻴﺖﻫﺎي ﻓﻌﺎل ﺷﺪه در اﺛﺮ IRﻛﻠﻴﻪ را در اﻳﺠـﺎد آﺳـﻴﺐ در ﻋـﻀﻮ
ﮔﻴﺮﻧـﺪه ﭘـﺲ از اﻧﺘﻘــﺎل ﻟﻜﻮﺳـﻴﺖﻫـﺎ در ﻧﺘــﺎﻳﺞ اﺧﻴـﺮ ﺣﺎﺻـﻞ از اﻳــﻦ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻫﻤﻜﺎران ﻛﺪﺧﺪاﻳﻲ و ﻣﻬﺮي Kadkhodaee M. et al.
76
اﻳﻦ ﻳﺎﻓﺘﻪﻫﺎ ﻟﻜﻮﺳﻴﺖﻫﺎ را ﺑﻪ ﻋﻨﻮان ﻳﻚ ﻋﺎﻣﻞ دﺧﻴﻞ در آﺳـﻴﺐ.ﻧﺪادﻧﺪ
آزﻣﺎﻳﺸﮕﺎه ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ ﻛﻠﻴﻪﻫﺎ ﻧﺴﺒﺘﺎ اﻋـﻀﺎي ﻣﻘـﺎومﺗـﺮي ﺑـﻮده و
. ﻛﻠﻴﻪ ﻣﻄﺮح ﻣﻲﻧﻤﺎﻳﺪIR ﺑﺎﻓﺘﻲ و اﻟﻘﺎي اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ در آﺳﻴﺐ
ﺗﺰرﻳﻖ ﺗﻌﺪاد ﻳﻜﺴﺎن ﻟﻜﻮﺳﻴﺖﻫـﺎي ﻓﻌـﺎل ﺷـﺪه ﻣﻮﺟـﺐ آﺳـﻴﺐﻫـﺎي
اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﺑﺨـﺸﻲ از ﻃـﺮح ﺗﺤﻘﻴﻘـﺎﺗﻲ ﺗﺤـﺖ:ﺳﭙﺎﺳﮕﺰاري
ﭼﺮا ﻛـﻪ ﻛﺒـﺪ ﭘﺬﻳﺮﻧـﺪه از.ﻓﺮاوانﺗﺮي در ﻛﺒﺪ ﻧﺴﺒﺖ ﺑﻪ ﻛﻠﻴﻪﻫﺎ ﻣﻲﺷﻮد
ﻋﻨﻮان "ﺑﺮرﺳﻲ آﺳﻴﺐ ﻛﻠﻴﻮي ﭘﺬﻳﺮﻧﺪه ﭘـﺲ از اﻧﺘﻘـﺎل ﻟﻜﻮﺳـﻴﺖﻫـﺎ از
ﻧﻈﺮ ﻋﻤﻠﻜﺮدي و ﺑﺎﻓﺘﻲ و اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ ﺗﻐﻴﻴﺮات ﺑﺴﻴﺎري را ﻧﺴﺒﺖ
" ﺧﻮنرﺳـﺎﻧﻲ ﻣﺠـﺪد ﻛﻠﻴـﻮي- ﻣﺒﺘﻼ ﺑﻪ اﻳﺴﻜﻤﻲInbred ﻣﻮش ﺳﻮري
ﻛﻠﻴـﻪﻫـﺎي، ﺣﺎل آنﻛﻪ در ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿـﺮ8.ﺑﻪ ﮔﺮوه ﺷﻢ ﮔﻴﺮﻧﺪه داﺷﺖ
ﺑﻪ ﻛﺪ1389 ﻣﺼﻮﺑﻪ و ﺑﺎ ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان در ﺳﺎل
ﭘﺬﻳﺮﻧﺪه ﻋﻠﻲرﻏﻢ اﻳﺠﺎد اﺳﺘﺮس اﻛﺴﻴﺪاﺗﻴﻮ و آﻏﺎز ﺗﻐﻴﻴﺮات ﭘﺎﺗﻮﻟﻮژﻳـﻚ
. ﻣﻲﺑﺎﺷﺪ10991
)ﺑﺎﻓﺖﺷﻨﺎﺳﻲ( از ﻧﻈﺮ ﻋﻤﻠﻜﺮدي ﺗﻔﺎوت ﭼﻨﺪاﻧﻲ ﺑـﺎ ﮔـﺮوه ﺷـﻢ ﻧـﺸﺎن
References 1.
Hassoun HT, Grigoryev DN, Lie ML, Liu M, Cheadle C, Tuder RM, et al. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol 2007;293(1):F30-40. 2. Lee HT, Kim M, Kim M, Kim N, Billings FT 4th, D'Agati VD, et al. Isoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice. Am J Physiol Renal Physiol 2007;293(3):F713-22. 3. Zhang ZX, Wang S, Huang X, Min WP, Sun H, Liu W, et al. NK cells induce apoptosis in tubular epithelial cells and contribute to renal ischemia-reperfusion injury. J Immunol 2008;181(11):7489-98. 4. Mizutani A, Okajima K, Uchiba M, Noguchi T. Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation. Blood 2000;95(12):37817. 5. Kanoria S, Jalan R, Seifalian AM, Williams R, Davidson BR. Protocols and mechanisms for remote ischemic preconditioning: a novel method for reducing ischemia reperfusion injury. Transplantation 2007;84(4):445-58. 6. Liu M, Liang Y, Chigurupati S, Lathia JD, Pletnikov M, Sun Z, et al. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol 2008;19(7):1360-70. 7. Serteser M, Koken T, Kahraman A, Yilmaz K, Akbulut G, Dilek ON. Changes in hepatic TNF-alpha levels, antioxidant status, and oxidation products after renal ischemia/reperfusion injury in mice. J Surg Res 2002;107(2):234-40. 8. Golab F, Kadkhodaee M, Zahmatkesh M, Hedayati M, Arab H, Schuster R, et al. Ischemic and non-ischemic acute kidney injury cause hepatic damage. Kidney Int 2009;75(8):783-92. 9. Chen WT, Huang WH, Wang D, Yu FC, Chi YC, Wu JC, et al. The protective effect of adenosine triphosphate-MgCl2 on ischemia-reperfusion lung injury is leukocyte dependent. J Biomed Sci 2003;10(6 Pt 2):725-30. 10. Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, et al. Novel docosanoids inhibit brain ischemiareperfusion-mediated leukocyte infiltration and proinflammatory gene expression. J Biol Chem 2003;278(44):43807-17. 11. Harada N, Okajima K, Murakami K, Usune S, Sato C, Ohshima K, et al. Adenosine and selective A(2A) receptor agonists reduce ischemia/reperfusion injury of rat liver mainly by inhibiting
leukocyte activation. J Pharmacol Exp Ther 2000;294(3):1034-42. 12. Khastar H, Kadkhodaee M, Sadeghipour HR, Seifi B, Hadjati J, Delavari F, et al. Leukocyte involvement in renal reperfusioninduced liver damage. Ren Fail 2011;33(1):79-83. 13. Donnahoo KK, Meng X, Ayala A, Cain MP, Harken AH, Meldrum DR. Early kidney TNF-alpha expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion. Am J Physiol 1999;277(3 Pt 2):R922-9. 14. Meldrum KK, Meldrum DR, Meng X, Ao L, Harken AH. TNFalpha-dependent bilateral renal injury is induced by unilateral renal ischemia-reperfusion. Am J Physiol Heart Circ Physiol 2002;282(2):H540-6. 15. Mizutani A, Okajima K, Uchiba M, Isobe H, Harada N, Mizutani S, et al. Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. Blood 2003;101(8):3029-36. 16. Rabb H, Daniels F, O'Donnell M, Haq M, Saba SR, Keane W, et al. Pathophysiological role of T lymphocytes in renal ischemiareperfusion injury in mice. Am J Physiol Renal Physiol 2000;279(3):F525-31. 17. Park P, Haas M, Cunningham PN, Bao L, Alexander JJ, Quigg RJ. Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes. Am J Physiol Renal Physiol 2002;282(2):F352-7. 18. Burne-Taney MJ, Yokota-Ikeda N, Rabb H. Effects of combined Tand B-cell deficiency on murine ischemia reperfusion injury. Am J Transplant 2005;5(6):1186-93. 19. Cowan KM, Easton AS. Neutrophils block permeability increases induced by oxygen glucose deprivation in a culture model of the human blood-brain barrier. Brain Res 2010;1332:20-31. 20. Renner B, Strassheim D, Amura CR, Kulik L, Ljubanovic D, Glogowska MJ, et al. B cell subsets contribute to renal injury and renal protection after ischemia/reperfusion. J Immunol 2010;185(7):4393-400. 21. Demirbilek S, Karaman A, Baykarabulut A, Akin M, Gürünlüoglu K, Türkmen E, et al. Polyenylphosphatidylcholine pretreatment ameliorates ischemic acute renal injury in rats. Int J Urol 2006;13(6):747-53. 22. Burne-Taney MJ, Liu M, Ascon D, Molls RR, Racusen L, Rabb H. Transfer of lymphocytes from mice with renal ischemia can induce albuminuria in naive mice: a possible mechanism linking early injury and progressive renal disease? Am J Physiol Renal Physiol 2006;291(5):F981-6.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺑﺮاي2,ﭘﺎﻳﺶ روش ﻛﺎراﻳﻲ دو Tehran University Medical Journal; Vol.ﺗﺸﺨﻴﺺ 70, No. May 2012: 69-77
Recipient kidney damage after leukocyte transfer from inbred mice with renal ischemia-reperfusion injury
Abstract Mehri Kadkhodaee Ph.D.1* Hossein Khastar Ph.D.2 Behjat Seifi Ph.D.1 Atefeh Najafi M.Sc.3 Fatemeh Delavari M.Sc.1
Received: September 07, 2011 Accepted: January 23, 2012
Background: In a recent study, we were able to demonstrate a role for leukocyte transfer in the induction of liver damage in recipient mice after induction of IR (60 min of bilateral renal artery occlusion and 3 hrs reperfusion) injury in donors. The present
1- Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2- Department of Physiology, Faculty of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. 3- Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
study investigates the role of leukocyte transfer in the induction of kidney damage in recipient mice after induction of renal IR injury in donors. Methods: Mice were divided into two sham and renal IR groups. After anesthesia, leukocytes were isolated from blood and were transferred to the two recipient groups: the intact recipient mice received leukocytes from the sham donor group (Sham recipient) and the intact recipient mice that received leukocytes from IR donor group (IR recipient). After 24 hrs, the recipient mice were anesthetized and blood samples and renal tissues were collected. Results: Renal malondialdehyde (MDA) increased and glutathione and superoxide dismutase (SOD) decreased significantly in IR recipient group in comparison to sham recipient group. Although renal function tests, including BUN and plasma creatinine were significantly different between IR donor and sham donor groups, but they were not significantly different in two recipient groups. Renal tissues in IR donor group showed extensive damage compared to sham group, but in IR recipients’ kidneys, they were different from IR donor tissues despite being different from their respective sham group. Conclusion: These findings are suggestive of implication of leukocytes in renal tissue damage and oxidative stress after renal IR injury. Keywords: Ischemia-reperfusion injury, kidneys, leukocytes, oxidative stress.
*
Corresponding author: Department of Physiology, Faculty of Medicine, Tehran Medical Sciences University, Poursina St., Tehran, Iran. Tel: +98- 21- 64053288 E-mail: kadkhodm@tums.ac.ir
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
78-85 ،1391 اردﻳﺒﻬﺸﺖ ﺷﻤﺎره 2 ﺼﻪدوره ﺗﻬﺮان، ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻣﻮش ﺷﺪه ،در ران 70اﻳ،ﺠﺎد ﺗﺠﺮﺑﻲ ﭘﺰﺷﻜﻲﻢ ﻧﻘﻴ ﻋﻠﻮم ﺑﺮ ﺗﺮﻣﻴ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﺗﺎﺛﻴﺮ
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ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي و ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺗﺎﺛﻴﺮ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ ران ﻣﻮش ﺻﺤﺮاﻳﻲ
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/06/05 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/15 :
ﻏﻔﻮر ﻣﻮﺳﻮي *1،دارﻳﻮش ﻣﻬﺎﺟﺮي،
2
ﭼﻜﻴﺪه
3
ﻋﻠﻲ رﺿﺎﻳﻲ 1،ﻣﺤﻤﺪرﺿﺎ وﻟﻴﻠﻮ،
زﻣﻴﻨﻪ و ﻫﺪف :ﺗﺮﻣﻴﻢ اﺳﺘﺨﻮان ،ﻳﻜﻲ از ﻣﺴﺎﻳﻞ ﭼﺎﻟﺶﺑﺮاﻧﮕﻴﺰ ﺟﺮاﺣﺎن از زﻣﺎنﻫﺎي دور ﺑﻮده اﺳﺖ .داروﻫـﺎي اﺳـﺘﺎﺗﻴﻨﻲ
4
آرﻣﺎن ﻋﻠﻴﻤﺤﻤﺪي
ﺑﻪ ﻋﻨﻮان ﭘﺎﻳﻴﻦ آورﻧﺪه ﻛﻠﺴﺘﺮول ﺧﻮن داراي اﺛﺮات ﻣﻔﻴﺪ در ﺗﺮﻣﻴﻢ اﺳﺘﺨﻮان ﻣﻲﺑﺎﺷﻨﺪ .ﻫﺪف اﻳﻦ ﻣﻄﺎﻟﻌﻪ ارزﻳـﺎﺑﻲ ﺗـﺎﺛﻴﺮ -1ﮔﺮوه ﺟﺮاﺣﻲ داﻣﭙﺰﺷﻜﻲ ،ﮔﺮوه ﻋﻠﻮم
آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ روﻧﺪ اﺳﺘﺨﻮانﺳﺎزي در ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ ﻓﻤﻮر ﻣﻮش ﺻﺤﺮاﻳﻲ ﻣﻲﺑﺎﺷـﺪ.
درﻣﺎﻧﮕﺎﻫﻲ ،داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ ،داﻧﺸﮕﺎه آزاد
روش ﺑﺮرﺳﻲ :اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺗﺠﺮﺑﻲ آزﻣﺎﻳﺸﮕﺎﻫﻲ ﺑﺮ روي 30ﺳﺮ ﻣﻮش ﺻﺤﺮاﻳﻲ ﻧﺮ ﻧـﮋاد SDاﻧﺠـﺎم ﺷـﺪ .ﻣـﻮشﻫـﺎ ﺑـﻪ
اﺳﻼﻣﻲ ،واﺣﺪ ﺗﺒﺮﻳﺰ ،ﺗﺒﺮﻳﺰ ،اﻳﺮان. -2ﮔﺮوه ﭘﺎﺗﻮﺑﻴﻮﻟﻮژي ،داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ،
ﺻﻮرت ﺗﺼﺎدﻓﻲ ﺑﻪ ﺳﻪ ﮔﺮوه )آزﻣﺎﻳﺶ و ﺷﺎﻫﺪ( ﺗﻘﺴﻴﻢ ﺷﺪﻧﺪ .ﭘﺲ از اﻟﻘﺎي ﺑﻴﻬﻮﺷﻲ ،ﺳﻮراﺧﻲ ﺑﻪ ﻗﻄﺮ دو ﻣﻴﻠﻲﻣﺘـﺮ در
داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ،واﺣﺪ ﺗﺒﺮﻳﺰ ،ﺗﺒﺮﻳﺰ ،اﻳﺮان
ﻋﺮض اﺳﺘﺨﻮان ران اﻳﺠﺎد ﺷﺪ .ﮔﺮوه ﺷﺎﻫﺪ ﻳﻚ ﻣﻴﻠﻲﻟﻴﺘﺮ ﺳﺮم ﻓﻴﺰﻳﻮﻟﻮژي و ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ ﻳﻚ و دو ﺑﻪ ﺗﺮﺗﻴﺐ 10
-3ﮔﺮوه داﻣﭙﺰﺷﻜﻲ ،داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ،واﺣﺪ
و 20ﻣﻴﻠﻲﮔﺮم ﺑﻪ ازاي ﻛﻴﻠﻮﮔﺮم آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﻪ ﺻﻮرت ﺧﻮراﻛﻲ درﻳﺎﻓﺖ ﻧﻤﻮدﻧﺪ 45 .روز ﺑﻌﺪ ،ﻣﻮشﻫﺎ آﺳـﺎن ﻛـﺸﻲ
ﺷﺒﺴﺘﺮ ،ﺷﺒﺴﺘﺮ ،اﻳﺮان -4ﮔﺮوه داﻣﭙﺰﺷﻜﻲ ،داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ ،داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ،واﺣﺪ ﺗﺒﺮﻳﺰ ،ﺗﺒﺮﻳﺰ ،اﻳﺮان
ﺷﺪه و ﻣﻘﺎﻃﻊ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژﻳﻚ از ﻣﺤﻞ ﻧﻘﻴﺼﻪ ﺗﻬﻴﻪ و ﻣﻮرد ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي و ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﻗﺮار ﮔﺮﻓـﺖ. ﻳﺎﻓﺘﻪﻫﺎ :در ﮔﺮوه ﺷﺎﻫﺪ ﻣﺤﻞ ﻧﻘﻴﺼﻪ ﺗﻮﺳﻂ اﺳـﺘﺨﻮان ﻧﺎﺑـﺎﻟﻎ ﺑـﻪ ﻫﻤـﺮاه ﻓـﻀﺎﻫﺎﻳﻲ از ﻣﻐـﺰ اﺳـﺘﺨﻮان ﭘـﺮ ﺷـﺪه ﺑـﻮد و اﺳﺘﺨﻮانﺳﺎزي ﺿﻌﻴﻔﻲ در ﻣﺤﻞ ﻧﻘﻴﺼﻪ ﻗﺎﺑﻞ ﻣﺸﺎﻫﺪه ﺑﻮد .در ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ ،ﻣﻘﺎدﻳﺮ ﻓﺮاوان اﺳﺘﺌﻮﺑﻼﺳﺖ ﺑـﻪ ﻫﻤـﺮاه ﺗﻌﺪاد زﻳﺎدي ﺗﺮاﺑﻜﻮلﻫﺎي اﺳﺘﺨﻮاﻧﻲ ﺟﻮان ﻗﺎﺑﻞ ﻣﺸﺎﻫﺪه ﺑﻮد ﻛﻪ ﺳـﺎزﻣﺎن ﻳﺎﻓﺘـﻪ ﺑـﻪ ﻧﻈـﺮ ﻣـﻲرﺳـﻴﺪﻧﺪ .ﻧﺘـﺎﻳﺞ ارزﻳـﺎﺑﻲ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﻧﺸﺎن داد ﻛﻪ آﺗﻮرواﺳﺘﺎﺗﻴﻦ داراي ﺗﺎﺛﻴﺮ ﻣﻌﻨﻲداري در اﻟﺘﻴﺎم اﺳﺘﺨﻮان در ﮔﺮوهﻫﺎي ﻣﻮرد آزﻣـﺎﻳﺶ دوم و ﺳﻮم ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺷﺎﻫﺪ ﻣﻲﺑﺎﺷﺪ ) ،(P<0/0001ارزﻳﺎﺑﻲ ﻧﺘﺎﻳﺞ ﺑﻪ دﺳﺖ آﻣﺪه ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑـﺎ دوز
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ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﺒﺮﻳﺰ ،ﺿﻠﻊ ﺷﺮﻗﻲ اﺗﻮﺑﺎن ﭘﺎﺳﺪاران،
داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ واﺣﺪ ﺗﺒﺮﻳﺰ ،داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ، ﮔﺮوه ﻋﻠﻮم درﻣﺎﻧﮕﺎﻫﻲ ،ﺑﺨﺶ ﺟﺮاﺣﻲ و رادﻳﻮﻟﻮژي
ﺑﺎﻻ در ﮔﺮوه ﺳﻮم داراي ﺗﺎﺛﻴﺮ ﻣﻌﻨﻲداري ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه دوم ﻣﻲﺑﺎﺷﺪ ) .(P<0/0001ﻧﺘﻴﺠﻪﮔﻴﺮي :ﻧﺘﺎﻳﺞ ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﻗﺎدر ﺑﻪ ﺗﺤﺮﻳﻚ اﺳﺘﺨﻮانﺳﺎزي در ﻣﻮش ﺻﺤﺮاﻳﻲ ﻣﻲﺑﺎﺷﺪ.
ﺗﻠﻔﻦ0411-6372274 : E-mail: gh_mousavi@iaut.ac.ir
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :آﺗﻮرواﺳﺘﺎﺗﻴﻦ ،اﻟﺘﻴﺎم اﺳﺘﺨﻮان ،ﻣﻮش ﺻﺤﺮاﻳﻲ ،ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي ،ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي.
ﻣﻘﺪﻣﻪ
آزﻣﺎﻳﺶ ،ﺗﺎﺛﻴﺮ ﻋﺎﻣﻞ زﻣﺎن را در ﺗﺮﻣﻴﻢ ﺷﻜﺴﺘﮕﻲ اﺳﺘﺨﻮان ﺗﺎﻳﻴﺪ ﻛﺮدﻧﺪ، ﺑﻪ اﻳﻦ ﺻﻮرت ﻛﻪ ﻫﺮ ﭼﻪ اﻟﺘﻴﺎم ﺳﺮﻳﻊﺗﺮ ﺷﻜﻞ ﺑﮕﻴﺮد ،ﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ
ﺑﺎ وﺟﻮد ﭘﻴﺸﺮﻓﺖﻫﺎي ﻓﺮاواﻧﻲ ﻛﻪ در ﺟﺮاﺣﻲ اﺳﺘﺨﻮان اﻳﺠﺎد ﺷﺪه
از ﻗﻮام و اﺳﺘﺤﻜﺎم ﺑﻴﺶﺗﺮي ﺑﺮﺧﻮردار ﺧﻮاﻫـﺪ ﺑـﻮد و اﺣﺘﻤـﺎل ﺑـﺮوز
اﺳﺖ ،وﻟﻲ اﻟﺘﻴﺎم اﺳﺘﺨﻮان ) (Bone healingﻧﺎﺷﻲ از ﺗﺮوﻣـﺎ ﻳـﺎ ﻋﻮاﻣـﻞ
ﻋﺪم ﺟﻮشﺧﻮردﮔﻲ ﻳﺎ ﺟﻮشﺧﻮردﮔﻲ ﺑﺎ ﺗﺎﺧﻴﺮ ﻛﻢﺗﺮ ﺷﺪه و ﻧﻴﺰ ﺑﺮوز 1-3
دﻳﮕﺮي ﻧﻈﻴـﺮ ﺗﻮﻣﻮرﻫـﺎي اﺳـﺘﺨﻮاﻧﻲ ﻳـﻚ ﻣـﺴﺌﻠﻪ ﭼـﺎﻟﺶ ﺑﺮاﻧﮕﻴـﺰ در
ﻋﻔﻮﻧﺖ و ﻋﺪم ﻣﻮﻓﻘﻴﺖ در ﺟﺮاﺣﻲ ارﺗﻮﭘﺪي ﻛﻢﺗﺮ ﺧﻮاﻫﺪ ﺷﺪ.
ﺟﺮاﺣﻲﻫﺎي ارﺗﻮﭘﺪي ﻣﻲﺑﺎﺷـﺪ .ﺗﺤﻘﻴﻘـﺎت اﻧﺠـﺎم ﮔﺮﻓﺘـﻪ روي ﺗـﺮﻣﻴﻢ
اﻳﻦ ﺳﻮال ﭘﻴﺶ ﻣﻲآﻳﺪ ﻛﻪ آﻳﺎ ﻣﻲﺗﻮان از دارو ﻳﺎ داروﻫﺎﻳﻲ اﺳﺘﻔﺎده ﻛـﺮد
ﺷﻜﺴﺘﮕﻲﻫﺎي اﺳﺘﺨﻮاﻧﻲ ،ﺑﻴﺎنﮔﺮ اﻳﻦ ﻣﻮﺿﻮع اﺳﺖ ﻛﻪ ﻋﺎﻣﻞ زﻣـﺎن در
ﻛﻪ زﻣـﺎن اﻟﺘﻴـﺎم را ﻛـﺎﻫﺶ دﻫـﺪ؟ آﺗﻮرواﺳـﺘﺎﺗﻴﻦ ) (Atorvastatinﻳـﻚ
روﻧﺪ ﺑﻬﺒﻮدي ﻣﻮﺛﺮ ﻣـﻲﺑﺎﺷـﺪ .اﻳـﻦ ﻧﺘﻴﺠـﻪ ،ﺣﺎﺻـﻞ اﻧﺠـﺎم آزﻣﺎﻳـﺸﺎت
داروي اﺳﺘﺎﺗﻴﻨﻲ و ﺗﻨﻈﻴﻢﻛﻨﻨﺪه ﭼﺮﺑﻲ ﺧﻮن ﺑﺎ ﻋﻤﻠﻜﺮد روي ﭼﺮﺑﻲﻫـﺎي
ﺧﻮاص ﻣﻜﺎﻧﻴﻜﻲ و رادﻳﻮﮔﺮاﻓﻲ ﻧﺎﺣﻴﻪ ﺷﻜﺴﺘﮕﻲ ﺑﻮده ﻛﻪ ﻫـﺮ دو ﻧـﻮع
ﭘﻼﺳﻤﺎﺳــﺖ .داروﻫــﺎي اﺳــﺘﺎﺗﻴﻨﻲ ﻣﻬﺎرﻛﻨﻨــﺪهﻫــﺎي رﻗــﺎﺑﺘﻲ آﻧــﺰﻳﻢ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺣﺎل
ﻏﻔﻮر ﻣﻮﺳﻮي و ﻫﻤﻜﺎران
79
)Hydroxymethyl Glutaryl CoA Reductase (HMG-CoA reductase
ﺑﺎﻟﻎ ﻧﮋاد ) Sprague-Dawley (SDﺑﺎ وزن ﺗﻘﺮﻳﺒﻲ 250-300ﮔﺮم و ﺳﻦ
ﻫﺴﺘﻨﺪ .اﻣﺮوزه اﻳﻦ داروﻫﺎ ﻛﺎرﺑﺮد وﺳﻴﻌﻲ در درﻣﺎن ﺑﻴﻤﺎريﻫـﺎي ﻗﻠﺒـﻲ
10ﻫﻔﺘــﻪ در ﺳــﺎل 1389در ﻣﺮﻛــﺰ ﺗﺤﻘﻴﻘــﺎت داﻧــﺸﻜﺪه داﻣﭙﺰﺷــﻜﻲ
ﻋﺮوﻗﻲ دارﻧﺪ 4.ﻣﻄﺎﻟﻌﺎت اﻧﺠﺎم ﺷﺪه روي ﺗﺮﻛﻴﺒﺎت اﺳﺘﺎﺗﻴﻨﻲ ﻧﺸﺎندﻫﻨﺪه
داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ﺗﺒﺮﻳﺰ اﻧﺠﺎم ﮔﺮﻓﺖ .ﻣـﻮشﻫـﺎ از ﻣﺮﻛـﺰ ﭘـﺮورش
ﺗﺎﺛﻴﺮ اﻳﻦ ﺗﺮﻛﻴﺒﺎت ﺑﺮ اﺳﺘﺨﻮان ﻣـﻲﺑﺎﺷـﺪ .اﻓـﺰاﻳﺶ اﺳـﺘﺨﻮانﺳـﺎزي و
ﺣﻴﻮاﻧﺎت آزﻣﺎﻳﺸﮕﺎﻫﻲ داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ﺗﺒﺮﻳـﺰ
ﺟﻠﻮﮔﻴﺮي از ﺑﺎزﺟﺬب اﺳﺘﺨﻮاﻧﻲ ﺗﻮﺳﻂ ﺗﺮﻛﻴﺒـﺎت اﺳـﺘﺎﺗﻴﻦ ﻧـﺸﺎن داده
ﺗﻬﻴﻪ ﮔﺮدﻳﺪﻧﺪ و ﭘﺲ از اﻧﺘﻘﺎل ﺑﻪ ﺑﺨﺶ ﺟﺮاﺣـﻲ ﺑـﻪ ﻣﻨﻈـﻮر ﭘﺮﻫﻴـﺰ از
ﺷﺪه اﺳﺖ6.و 5ﺗﺮﻛﻴﺒﺎت اﺳﺘﺎﺗﻴﻨﻲ داراي اﺛﺮات ﺿﺪاﻟﺘﻬﺎﺑﻲ ﺑﻮده و اﻳﻦ اﺛﺮ
اﺳﺘﺮس و ﺳﺎزﮔﺎر ﺷﺪن ﺑﺎ ﻣﺤﻴﻂ ﻫﻴﭻﮔﻮﻧـﻪ آزﻣﺎﻳـﺸﻲ ﺑـﻪ ﻣـﺪت ﻳـﻚ
را ﺑﺎ ﻛﺎﻫﺶ اﻳﻨﺘﺮﻟﻮﻛﻴﻦ 6 -و اﻳﻨﺘﺮﻟﻮﻛﻴﻦ 8 -اﻋﻤﺎل ﻣـﻲﻧﻤﺎﻳﻨـﺪ 7.اوﻟـﻴﻦ
ﻫﻔﺘﻪ روي آنﻫﺎ ﺻﻮرت ﻧﮕﺮﻓﺖ .ﻣﻮشﻫﺎ در درﺟﻪ ﺣـﺮارت 23±2 ºC
ﺑﺎر Mundyدر ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﺗﺠﺮﺑﻲ ﮔﺰارش ﻛﺮد ﻛـﻪ اﺳـﺘﺎﺗﻴﻦﻫـﺎ ﺗـﺎﺛﻴﺮ
و رﻃﻮﺑﺖ ﻧﺴﺒﻲ ﻫﻔﺘﺎد درﺻﺪ و ﭼﺮﺧﻪ روﺷﻨﺎﻳﻲ -ﺗﺎرﻳﻜﻲ 12ﺳـﺎﻋﺖ
ﻣﺜﺒﺘــﻲ در ﺣﺠــﻢ اﺳــﺘﺨﻮان دارﻧــﺪ .در اﻳــﻦ ﻣﻄﺎﻟﻌــﻪ ﺣﺠــﻢ اﺳــﺘﺨﻮان
و در ﻗﻔﺲﻫﺎي ﺟﺪاﮔﺎﻧﻪ ﻧﮕﻪداري ﺷﺪﻧﺪ .ﺗﻐﺬﻳﻪ ﺑﺎ اﺳﺘﻔﺎده از ﭘﻠﺖ آﻣﺎده
ﺗﺮاﺑﻜﻮﻻر در ﻧﻤﻮﻧﻪﻫﺎي رتﻫﺎﻳﻲ ﻛﻪ ﺗﺨﻤـﺪان آنﻫـﺎ ﺑﺮداﺷـﺘﻪ ﺷـﺪه و
ﻣﺨﺼﻮص ﺣﻴﻮاﻧﺎت آزﻣﺎﻳﺸﮕﺎﻫﻲ ﺻﻮرت ﮔﺮﻓﺘﻪ و آب ﻧﻴﺰ ﺑﻪ ﻃﻮر آزاد
روزاﻧﻪ ﺑﻪ ﻣﺪت 35روز ﺳﻴﻤﻮاﺳـﺘﺎﺗﻴﻦ ﺑـﺎ دوز ﭘـﻨﺞ ﺗـﺎ 10ﻣﻴﻠـﻲﮔـﺮم
در اﺧﺘﻴﺎر ﺣﻴﻮاﻧﺎت ﻗﺮار ﮔﺮﻓﺖ .ﻣﻮشﻫﺎ ﺑﻪ ﺻـﻮرت ﺗـﺼﺎدﻓﻲ ﺑـﻪ ﺳـﻪ
درﻳﺎﻓﺖ ﻛﺮدﻧﺪ ،اﻓﺰاﻳﺶ ﻳﺎﻓﺘﻪ ﺑﻮد 5.ﻣﻄﺎﻟﻌﺎت زﻳﺎدي ﺑـﺮاي اﺛﺒـﺎت ﺗـﺎﺛﻴﺮ
ﮔﺮوه ﺑﺮاﺑﺮ ﺑﺎ 10ﺳﺮ ﻣﻮش در ﻫﺮ ﮔﺮوه ﺗﻘـﺴﻴﻢ ﺷـﺪﻧﺪ .ﭘﺮوﺗﻜـﻞ اﻳـﻦ
ﺗﻘﻮﻳﺘﻲ اﺳﺘﺨﻮان در ﻛﺎرﺑﺮد ﻣﻮﺿﻌﻲ اﺳﺘﺎﺗﻴﻦﻫﺎ در ﻧﻤﻮﻧﻪﻫـﺎي ﺣﻴـﻮاﻧﻲ
ﻣﻄﺎﻟﻌﻪ ﻣﻄﺎﺑﻖ اﺻﻮل اﺧﻼﻗﻲ ﻣﻮرد ﺗﺎﻳﻴﺪ ﻛﻤﻴﺘﻪﻫﺎي ﺑﻴﻦاﻟﻤﻠﻠﻲ ﺣﻤﺎﻳـﺖ
اﻧﺠﺎم ﺷﺪه اﺳﺖ .در اﻳـﻦ زﻣﻴﻨـﻪ ﺗـﺎﺛﻴﺮ ﺳﻴﻤﻮاﺳـﺘﺎﺗﻴﻦ ،ﻳﻜـﻲ دﻳﮕـﺮ از
از ﺣﻘﻮق ﺣﻴﻮاﻧﺎت آزﻣﺎﻳﺸﮕﺎﻫﻲ ﻃﺮاﺣﻲ ﺷﺪه اﺳﺖ.
داروﻫــﺎي اﺳــﺘﺎﺗﻴﻨﻲ ،در اﻓــﺰاﻳﺶ ﺣﺠــﻢ ﺑﺎﻓــﺖ اﺳــﺘﺨﻮان ،ﺳــﺮﻋﺖ ﺷﻜﻞﮔﻴﺮي اﺳﺘﺨﻮان و اﺳﺘﺤﻜﺎم ﺑﺎﻓﺖ اﺳﻔﻨﺠﻲ اﺳﺘﺨﻮان ﺛﺎﺑﺖ ﮔﺮدﻳﺪه
ﺑﻪ ﻣﻨﻈـﻮر اﻳﺠـﺎد ﺑﻴﻬﻮﺷـﻲ از ﻛﺘـﺎﻣﻴﻦ
(Ketamine 10%, Alfasan,
) Woerden-Hollandﺑـﻪ ﻣﻴـﺰان 50mg/kgو زاﻳﻼزﻳـﻦ
(Xylazin 2%,
اﺳﺖ 8.در زﻣﻴﻨﻪ ﺗﺮﻛﻴﺒﺎت اﺳﺘﺎﺗﻴﻦ و ﻣﺘﺎﺑﻮﻟﻴﺴﻢ اﺳﺘﺨﻮان ،ﭼﻨﺪ ﻣﻜﺎﻧﻴﺴﻢ
)Woerden-Holland
ﻣﻮرد ﺗﻮﺟﻪ ﻣﻲﺑﺎﺷﺪ .اﻳﻦ ﺗﺮﻛﻴﺒﺎت ﺑﺎ اﻓﺰاﻳﺶ ﻓﻌﺎﻟﻴﺖ اﺳﺘﺌﻮﺑﻼﺳـﺖ ﻛـﻪ
ﺻﻔﺎﻗﻲ اﺳﺘﻔﺎده ﺷﺪ .ﭘﺲ از اﻳﺠﺎد ﺑﻴﻬﻮﺷﻲ ،ﻧﺎﺣﻴﻪ ﺳﺘﻴﻎ ﻟﮕﻨﻲ ﺗﺎ ﻣﻔﺼﻞ
ﺗﻮﺳﻂ BMP-2اﻋﻤﺎل ﻣﻲﺷﻮد ﺳﺒﺐ ﺗﺤﺮﻳﻚ اﺳﺘﺨﻮانﺳﺎزي ﻣﻲﺷـﻮﻧﺪ.
زاﻧﻮي اﻧﺪام ﺣﺮﻛﺘﻲ ﺧﻠﻔﻲ ﭼﭗ ﺑـﻪ ﺻـﻮرت ﻣﻌﻤـﻮل آﻣـﺎده ﺟﺮاﺣـﻲ
اﺛﺮ دﻳﮕﺮ اﺳﺘﺎﺗﻴﻦ ﻫﺎ ﻣﻬﺎر آﻧﺰﻳﻢ ﻫﻴﺪروﻛـﺴﻲﻣﺘﻴـﻞﮔﻠﻮﺗﺎرﻳـﻞﻛـﻮآﻧﺰﻳﻢ-آ
ﮔﺮدﻳﺪ .ﺑﺮﺷﻲ ﺑﻪ ﻃﻮل ﺳﻪ ﺳﺎﻧﺘﻲﻣﺘﺮ روي ﭘﻮﺳﺖ ﺑﺨـﺶ ﺟـﺎﻧﺒﻲ اﻧـﺪام
ردوﻛﺘﺎز و ﺟﻠﻮﮔﻴﺮي از ﺳﻨﺘﺰ ﻣﻮاﻟﻮﻧﺎت اﺳﺖ ﻛﻪ ﺳﺒﺐ اﺧﺘﻼل ﻓﻌﺎﻟﻴـﺖ
ﺧﻠﻔﻲ ﭼﭗ ﺑﻪ ﻣﻮازات اﺳﺘﺨﻮان ﻓﻤﻮر اﻳﺠﺎد ﺷﺪ .ﻓﺎﺷـﻴﺎ و ﺑﺎﻓـﺖﻫـﺎي
اﺳﺘﺌﻮﻛﻼﺳﺖﻫﺎ و اﻓﺰاﻳﺶ آﭘﻮﭘﺘﻮزﻳﺲ آنﻫـﺎ ﻣـﻲﮔـﺮدد و ﺳـﺮاﻧﺠﺎم از
ﻫﻤﺒﻨﺪي زﻳﺮ ﺟﻠﺪي ﺑﻪ ﺻﻮرت ﻛُﻨـﺪﻛﺎري ﺟـﺪا و ﺳـﭙﺲ ﻋـﻀﻼت از
اﻓﺰاﻳﺶ ﺑﺎزﺟﺬب اﺳﺘﺨﻮاﻧﻲ ﺟﻠﻮﮔﻴﺮي ﻣﻲﻛﻨﺪ 9.ﺳﻮﻣﻴﻦ ﺗﺎﺛﻴﺮ ﺗﺮﻛﻴﺒـﺎت
ﻣﺤﻞ اﺗﺼﺎل آنﻫﺎ ﺑﻪ ﻫﻤﺪﻳﮕﺮ ﺑﺎز ﮔﺮدﻳﺪ و اﺳﺘﺨﻮان ﻓﻤـﻮر در ﻣﻌـﺮض
اﺳﺘﺎﺗﻴﻦ اﺛﺮ ﺿﺪ اﻟﺘﻬﺎﺑﻲ آنﻫﺎ ﻣﻲﺑﺎﺷﺪ ﻛﻪ در ﻫﻨﮕﺎم ﺷﻜﻞﮔﻴـﺮي ﻧﻘﻴـﺼﻪ
دﻳﺪ ﻗﺮار ﮔﺮﻓﺖ .ﺑﺎ اﺳﺘﻔﺎده از ﻣﺘـﻪ دﻧـﺪانﭘﺰﺷـﻜﻲ و ﺣـﺪاﻛﺜﺮ ﺳـﺮﻋﺖ
اﺳﺘﺨﻮاﻧﻲ در اﺳﺘﺨﻮان درﮔﻴﺮ و ﺑﺎﻓـﺖﻫـﺎي ﻣﺠـﺎور اﻟﺘﻬـﺎب ﺷـﺪﻳﺪي
ﭼﺮﺧﺶ 6000دور در دﻗﻴﻘﻪ ﺳﻮراﺧﻲ ﺑﻪ ﻗﻄﺮ دو ﻣﻴﻠﻲﻣﺘـﺮ در ﻋـﺮض
اﻳﺠﺎد ﻣﻲﺷﻮد ﻛﻪ اﻳﻦ اﺛﺮ اﺳﺘﺎﺗﻴﻦﻫﺎ ﻧﻴﺰ ﻣﻲﺗﻮاﻧـﺪ ﺑـﻪ ﺗـﺮﻣﻴﻢ اﺳـﺘﺨﻮان
اﺳﺘﺨﻮان ﻓﻤﻮر ﺗﺎ رﺳﻴﺪن ﺑﻪ ﻛﺎﻧﺎل ﻣﺪوﻻري اﻳﺠﺎد ﺷـﺪ .ﺑـﺎ اﻃﻤﻴﻨـﺎن از
ﻛﻤﻚ ﻧﻤﺎﻳﺪ 10.ﻫﺪف اﻳﻦ ﻣﻄﺎﻟﻌﻪ ارزﻳﺎﺑﻲ ﺗﺎﺛﻴﺮ آﺗﻮرواﺳـﺘﺎﺗﻴﻦ در اﻟﺘﻴـﺎم
ﻧﺤﻮه اﻧﺠﺎم ﺟﺮاﺣﻲ ،ﻣﻮﺿﻊ ﺑﺎ ﻧﺮﻣﺎل ﺳﺎﻟﻴﻦ ﺷﺴﺘﺸﻮ داده ﺷـﺪ .ﻧﻘﻴـﺼﻪ
ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ ﻓﻤـﻮر در ﻣـﺪل ﺣﻴـﻮاﻧﻲ ﻣـﻮش
اﻳﺠﺎد ﺷﺪه ﺑﻪ ﺻﻮرت ﺧﺎﻟﻲ رﻫﺎ ﺷﺪه و ﻋﻀﻼت ﻧﺎﺣﻴـﻪ ﺑـﺎ اﺳـﺘﻔﺎده از
ﺻــﺤﺮاﻳﻲ ﻣــﻲﺑﺎﺷــﺪ ﻛــﻪ ﺑــﻪ ﺻــﻮرت ارزﻳــﺎﺑﻲ ﻫﻴــﺴﺘﻮﭘﺎﺗﻮﻟﻮژي و
ﻧﺦ ﺑﺨﻴﻪ ﻗﺎﺑﻞ ﺟﺬب ﺳﻨﺘﺘﻴﻚ ﭘﻠﻲﮔﻠـﻲﻛـﻮﻻت
(Supa, Co, Iran) 0-4
ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي اﻧﺠﺎم ﺷﺪه اﺳﺖ.
اﻳﺮان ﺑﻪ ﺻﻮرت ﺳﺎده ﺳﺮﺗﺎﺳﺮي ﺑﺨﻴﻪ زده ﺷﺪ .ﭘﻮﺳﺖ ﻣﺤﻞ ﺑﺮش ﻧﻴـﺰ
Alfasan,ﺑﻪ ﻣﻴـﺰان 5mg/kgﺑـﻪ ﺻـﻮرت داﺧـﻞ
ﺗﻮﺳﻂ ﻧﺦ ﺑﺨﻴﻪ ﺳﻴﻠﻚ ﺳﻪ ﺻﻔﺮ ﺳﺎﺧﺖ ﻛﺎرﺧﺎﻧﻪ ﺳﻮﭘﺎ ﺑﻪ ﺻﻮرت ﺗﻜﻲ
روش ﺑﺮرﺳﻲ
ﺳﺎده ﺑﺨﻴﻪ ﮔﺮدﻳﺪ .ﺑﻌﺪ از ﺑﻪ ﻫﻮش آﻣﺪن ﻛﺎﻣﻞ ،ﺣﻴﻮاﻧﺎت ﺑﻪ ﻗﻔﺲﻫـﺎي ﻣﺨﺼﻮص ﺧﻮد اﻧﺘﻘـﺎل داده ﺷـﺪﻧﺪ و در اﺧﺘﻴﺎرﺷـﺎن آب و ﻏـﺬا ﻗـﺮار
اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﺗﺠﺮﺑـﻲ آزﻣﺎﻳﺸﮕﺎﻫﻲ روي 30ﺳﺮ ﻣﻮش ﺻﺤﺮاﻳﻲ ﻧﺮ
ﮔﺮﻓﺖ .ﺟﻬﺖ ﺟﻠﻮﮔﻴﺮي از ﻋﻔﻮﻧﺖﻫﺎي اﺣﺘﻤﺎﻟﻲ روزاﻧﻪ 40000واﺣـﺪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺗﺎﺛﻴﺮ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در ران ﻣﻮش
80
(Jaber-ebn-Hayanو 5mgﺟﻨﺘﺎﻣﺎﻳــﺴﻴﻦ
ﮔﺮدﻳﺪ .ﺑﻪ ﻣﻨﻈﻮر ﺗﻌﻴﻴﻦ ﻣﻘﺎدﻳﺮ ﻧﺮﻣﺎل اﺳﺘﺨﻮان ﻻﻣﻼر ،اﺳﺘﺨﻮان ﺗﻴﻐﻪاي
) (Alborz daru, Co , Iranﺑﻪ ازاي ﻫﺮ ﻛﻴﻠﻮﮔﺮم وزن ﺑـﺪن ﺑـﻪ ﺻـﻮرت
و ﻣﻐﺰ اﺳﺘﺨﻮان ،ﻗﻄﻌﻪ اﺳﺘﺨﻮاﻧﻲ ﺳﺎﻟﻢ اﻧﺪام ﺣﺮﻛﺘﻲ ﻣﻘﺎﺑﻞ ﻧﻴـﺰ ﺟـﺪا و
ﻋﻀﻼﻧﻲ ﺑﻪ ﻣﺪت ﭘﻨﺞ روز ﺗﺰرﻳﻖ ﺷﺪ .ﭘﺲ از اﻳﺠﺎد ﻧﻘﻴﺼﻪ اﺳـﺘﺨﻮاﻧﻲ
ﻣﻮرد ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﻗﺮار ﮔﺮﻓﺖ.
ﭘﻨــﻲﺳــﻴﻠﻴﻦ
Co, Iran) G
ﺑﻪ ﮔﺮوه اول ﻛﻪ ﺑﻪ ﻋﻨﻮان ﮔﺮوه ﺷﺎﻫﺪ در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪ ،ﻳﻚ ﻣﻴﻠﻲﻟﻴﺘـﺮ
ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻧﺘﺎﻳﺞ آزﻣﻮن ﻫﻤﮕـﻮﻧﻲ وارﻳـﺎﻧﺲﻫـﺎ و آزﻣـﻮن ﺗﻮزﻳـﻊ
ﺳﺮم ﻓﻴﺰﻳﻮﻟﻮژي ﺑﻪ ﻃﻮر روزاﻧﻪ و ﺑﻪ ﻣﺪت 45روز ﺑﻪ ﺻﻮرت ﺧﻮراﻛﻲ
ﻧﺮﻣﺎل دادهﻫﺎ ) (Kolmogorov-Smirnoffدادهﻫﺎي ﺑﻪدﺳﺖ آﻣـﺪه ﻛﻤـﻲ،
ﺗﻮﺳﻂ ﺳﻮﻧﺪ ﻣﺮي ﺧﻮراﻧﺪه ﺷﺪ .ﻫﻢﭼﻨﻴﻦ ﺑﻪ ﻣﻮشﻫﺎي ﮔﺮوهﻫـﺎي دوم
ﺑﻪ ﺻﻮرت ﻣﻴﺎﻧﮕﻴﻦ و اﻧﺤﺮاف اﺳﺘﺎﻧﺪارد اراﻳﻪ و اﺧﺘﻼف ﻣﻌﻨـﻲدار ﺑـﻴﻦ
و ﺳــﻮم ﻧﻴــﺰ ﭘــﺲ از اﻳﺠــﺎد ﻧﻘﻴــﺼﻪ اﺳــﺘﺨﻮاﻧﻲ ،ﺑــﻪ ﺗﺮﺗﻴــﺐ 10و 20
ﮔﺮوهﻫﺎ ﺗﻮﺳﻂ آزﻣﻮن آﻣﺎري آﻧﺎﻟﻴﺰ وارﻳـﺎﻧﺲ ﻳـﻚ ﻃﺮﻓـﻪ ) (ANOVAو
ﻣﻴﻠﻲﮔﺮم ﺑﻪ ازاي ﻫﺮ ﻛﻴﻠﻮﮔﺮم وزن ﺑﺪن داروي آﺗﻮرواﺳـﺘﺎﺗﻴﻦ )ﻗـﺮص
آزﻣﻮن ﺗﻌﻘﻴﺒﻲ ﺗﻮﻛﻲ ) (Tukeyو ،α=0/05در ﺳﻄﺢ ﻣﻌﻨﻲداري
آﺗﻮرواﺳﺘﺎﺗﻴﻦ 20ﻣﻴﻠـﻲﮔﺮﻣـﻲ ،ﺳـﺎﺧﺖ ﺷـﺮﻛﺖ
داروﺳـﺎزي Sobhan
P<0/05
ﺗﻮﺳﻂ ﺑﺴﺘﻪ ﻧﺮماﻓﺰاري SPSSوﻳﺮاﺳﺖ 18ﺑﺮآورد ﮔﺮدﻳﺪ.
دارو( ﻛﻪ در ﻳﻚ ﻣﻴﻠﻲﻟﻴﺘﺮ ﺳﺮم ﻓﻴﺰﻳﻮﻟﻮژي ﺗﻬﻴـﻪ ﺷـﺪه ﺑـﻮد ،ﺑـﻪ ﻃـﻮر روزاﻧﻪ و در ﻳﻚ ﺳﺎﻋﺖ ﻣﻌﻴﻦ ،ﺑﻪ ﻣـﺪت 45روز ﺗﻮﺳـﻂ ﺳـﻮﻧﺪ ﻣـﺮي ﺧﻮراﻧﺪه ﺷﺪ 11.ﻛﻠﻴﻪ ﻣﺮاﺣﻞ آزﻣﺎﻳﺶ )ﺷـﺎﻣﻞ ﺗﻴﻤـﺎر ،ﻧﻤﻮﻧـﻪﺑـﺮداري و ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي( ﺑﻪ ﺻﻮرت دوﺳﻮ ﺑﻲﺧﺒﺮ ﺷﺪ.
ﻳﺎﻓﺘﻪﻫﺎ ﻳﺎﻓﺘﻪﻫﺎي ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي :ارزﻳﺎﺑﻲ ﺟﺎﻳﮕـﺎه ﺗـﺮﻣﻴﻢ در ﻣـﻮشﻫـﺎي
ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي :ﺑﻪ ﻣﻨﻈﻮر ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي در روز
ﮔﺮوه ﺷﺎﻫﺪ 45روز ﭘﺲ از ﺟﺮاﺣﻲ ﻧﺸﺎن داد ﻛﻪ ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در
46ﭘﺲ از ﺟﺮاﺣﻲ ،ﻣﻮشﻫﺎ اﺑﺘﺪا ﺗﻮﺳﻂ اﺗﺮ ﺑﻴﻬـﻮش ﺷـﺪه ،ﺳـﭙﺲ ﺑـﺎ
ﻗﺴﻤﺖ ﻣﻴﺎﻧﻲ دﻳﺎﻓﻴﺰ اﺳﺘﺨﻮان ﻓﻤـﻮر ﺗﻮﺳـﻂ اﺳـﭙﻴﻜﻮلﻫـﺎي اﺳـﺘﺨﻮان
(Thiopental Sodium,
ﻧﺎﺑﺎﻟﻎ ﭘﺮ ﺷﺪه اﺳﺖ و ﻣﺎﺑﻴﻦ اﺳﺘﺨﻮانﻫﺎي ﺗﺎزه ﺗﺸﻜﻴﻞ ﻓﻀﺎﻫﺎي وﺳﻴﻌﻲ
) Trittau, Germanyﺑﻪ ﺻﻮرت داﺧﻞ ﺻﻔﺎﻗﻲ آﺳﺎنﻛﺸﻲ ﺷﺪﻧﺪ .ﺳـﭙﺲ
از ﻣﻐﺰ اﺳﺘﺨﻮان وﺟﻮد دارد .اﺳـﺘﺨﻮان ﺗـﺎزه ﺗـﺸﻜﻴﻞ ﻧﺎﺑـﺎﻟﻎ در ﻣﺤـﻞ
ﺑــﺮش در ﭘﻮﺳــﺖ اﻳﺠــﺎد ﺷــﺪه ،ﻓﺎﺳــﻴﺎ و ﻋــﻀﻼت از روي ﻛــﺎﻟﻮس
اﺗﺼﺎل آن ﺑﺎ اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ ،ﺗﻮﺳﻂ اﺳﺘﺨﻮان ﺗﻴﻐـﻪاي اوﻟﻴـﻪ در ﺣـﺎل
اﺳﺘﺨﻮاﻧﻲ ﻛﻨﺎر زده ﺷﺪ .اﺳﺘﺨﻮان ﻓﻤﻮر ﺟﺪا و در ﻣﺤﻠﻮل ﻓﺮﻣﺎﻟﻴﻦ ﺑـﺎﻓﺮ
ﺟﺎﻳﮕﺰﻳﻨﻲ ﻣﻲﺑﺎﺷﺪ )ﺷـﻜﻞ .(1در ﻣـﻮشﻫـﺎي ﮔـﺮوه دوم )ﺗﻴﻤـﺎر ﺑـﺎ
10درﺻﺪ ﻗﺮار داده ﺷﺪ .ﭘﺲ از ﭘﺎﻳﺪار ﺷﺪن ﻧﻤﻮﻧﻪﻫﺎ ،ﻛﻠـﺴﻴﻢﮔﻴـﺮي از
آﺗﻮرواﺳﺘﺎﺗﻴﻦ (10mg/kgﻻﻳﻪ ﺑﺎرﻳﻜﻲ از اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﻧﻘﻴـﺼﻪ اﻳﺠـﺎد
ﺑﺎﻓﺖ اﺳﺘﺨﻮان ﺗﻮﺳﻂ ﻣﺤﻠﻮل اﺳﻴﺪﻧﻴﺘﺮﻳﻚ 10درﺻﺪ اﻧﺠﺎم ﮔﺮدﻳـﺪ .از
ﺷــﺪه را ﻣــﺴﺪود ﻛــﺮده اﺳــﺖ و اﺳــﺘﺨﻮان ﻣﺘــﺮاﻛﻢ اوﻟﻴــﻪ در ﺣــﺎل
ﻫﺮ ﻧﻤﻮﻧﻪ ﺑﺮشﻫﺎي ﭘﻲدرﭘﻲ ﺑﻪ ﻗﻄـﺮ ﭘـﻨﺞ ﻣﻴﻜﺮوﻣﺘـﺮ از ﻣﺤـﻞ ﻧﻘﻴـﺼﻪ
ﺷﻜﻞﮔﻴﺮي ﻣـﻲﺑﺎﺷـﺪ و ﻓـﻀﺎﻫﺎي اﺳـﺘﺨﻮاﻧﻲ ﻣـﺎﺑﻴﻦ اﺳـﺘﺨﻮان ﻧﺎﺑـﺎﻟﻎ
اﺳﺘﺨﻮاﻧﻲ ﺗﻬﻴﻪ ﺷﺪ .ﻻمﻫﺎي ﺗﻬﻴﻪ ﺷﺪه ﺑﻪ روش ﻫﻤﺎﺗﻮﻛـﺴﻴﻠﻴﻦ اﺋـﻮزﻳﻦ
ﻣﺘﺮاﻛﻢﺗﺮ ﺷﺪهاﻧﺪ .ﻓﻀﺎﻫﺎي ﻣﻐﺰ اﺳـﺘﺨﻮاﻧﻲ ﻣـﺎﺑﻴﻦ ﺗﻴﻐـﻪ ﻫـﺎي ﻧﺎﺑـﺎﻟﻎ و
رﻧﮓآﻣﻴﺰي ﮔﺮدﻳﺪ و ﺑﺎ اﺳﺘﻔﺎده از ﻣﻴﻜﺮوﺳﻜﻮپ ﻧﻮري ﺳﺎﺧﺖ ﺷـﺮﻛﺖ
ﻣﺘﺮاﻛﻢ اوﻟﻴﻪ ﺗﺎزه ﺗﺸﻜﻴﻞ ﻫﻢﭼﻨـﺎن ﺑـﺎﻗﻲ ﺑـﻮده ،ﺑﺎﻓـﺖ اﺳـﺘﺨﻮان ﺗـﺎزه
ﻧﻴﻜﻮن ﻣـﺪل ) (ECLIPSE E200, Japanﻣـﻮرد ﻣﻄﺎﻟﻌـﻪ ﻫﻴـﺴﺘﻮﭘﺎﺗﻮﻟﻮژي
ﺗﺸﻜﻴﻞ از ﺗـﺮاﻛﻢ ﺑـﻪ ﻧـﺴﺒﺖ ﺑـﻴﺶﺗـﺮي در ﻣﻘﺎﻳـﺴﻪ ﺑـﺎ ﮔـﺮوه ﺷـﺎﻫﺪ
ﻗﺮار ﮔﺮﻓﺖ.
ﺑﺮﺧﻮردار ﻣﻲ ﺑﺎﺷﺪ )ﺷﻜﻞ .(2در ﻣـﻮشﻫـﺎي ﮔـﺮوه ﺳـﻮم )ﺗﻴﻤـﺎر ﺑـﺎ
ﺗﺰرﻳﻖ دوز ﺑﺎﻻي ) (20mg/kgﺗﻴﻮﭘﻨﺘﺎل ﺳـﺪﻳﻢ
ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي :ﺑﺮاي ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺗﻮﺳـﻂ
آﺗﻮرواﺳﺘﺎﺗﻴﻦ (20mg/kgﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ ﺗﻘﺮﻳﺒﺎ ﺑﻪ ﺻﻮرت ﻛﺎﻣـﻞ ﺑـﺎ
اﻧﺪازهﮔﻴﺮي ﺧﻄـﻲ از ﻃﺮﻳـﻖ ﺧﻄـﻮط ﻣـﺸﺒﻚ ﻣﺘﻘـﺎﻃﻊ و ﺗﻮﺳـﻂ ﻳـﻚ
اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ ﭘﺮ ﺷﺪه اﺳﺖ و ﻧﺴﺒﺖ ﺑـﻪ ﮔـﺮوه 10ﻣﻴﻠـﻲﮔـﺮم
ﻋﺪﺳﻲ ﭼﺸﻤﻲ ﻣﺸﺒﻚ ،ﺣﺎوي 100ﺧﺎﻧﻪ ﻣﺮﺑﻌﻲ ،ﺑﺎ ﺗﻌﻴﻴﻦ درﺻـﺪي از
اﺳﺘﺨﻮان ﺷﻜﻞ ﮔﺮﻓﺘﻪ ﻣﺘﺮاﻛﻢﺗﺮ و ﺳﺎزﻣﺎن ﻳﺎﻓﺘﻪﺗﺮ ﻣﻲﺑﺎﺷـﺪ و ﻓـﻀﺎﻫﺎي
ﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ ﻛﻪ ﺗﻮﺳﻂ (1ﻣﻐـﺰ اﺳـﺘﺨﻮان (2 ،اﺳـﺘﺨﻮان ﻧﺎﺑـﺎﻟﻎ و
ﻣﺎﺑﻴﻦ اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ ﺑﻪ ﻫﻢ ﻓﺸﺮده ﺷـﺪه و ﺗﻘﺮﻳﺒـﺎ از ﺑـﻴﻦ رﻓﺘـﻪ
(3اﺳﺘﺨﻮان ﻻﻣﻼر اﺷﻐﺎل ﺷﺪه ﺑﻮد ،ﺻﻮرت ﭘﺬﻳﺮﻓﺖ 12.اﺟـﺰاي ﺑـﺎﻓﺘﻲ
اﺳﺖ .در ﻧﻤﺎي ﻧﺰدﻳﻚﺗﺮ از ﻣﻴﺰان اﺳﺘﺨﻮانﻫﺎي ﻧﺎﺑـﺎﻟﻎ )ﺗﺮاﺑﻜـﻮلﻫـﺎي
ﻣﺬﻛﻮر ﺑﺎ ﺑﺰرگﻧﻤﺎﻳﻲ ×40و ﻧﺸﺎنﮔﺮ ﻣﺎوس ،ﺗﻌﻴـﻴﻦ و ﻣـﻮرد ﺳـﻨﺠﺶ
ﻧﺎﻣﻨﻈﻢ( ﻛﺎﺳﺘﻪ ﺷﺪه اﺳﺖ و ﻗـﺴﻤﺖ اﻋﻈـﻢ ﻧﻘﻴـﺼﻪ اﺳـﺘﺨﻮاﻧﻲ ﺗﻮﺳـﻂ
ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﻣﻐﺰ اﺳﺘﺨﻮان ﺑﺎ ﺳﻠﻮلﻫﺎي ﭼﺮﺑﻲ ﻓﺮاوان و ﺑﺎﻓﺖ ﻫﻤﺒﻨﺪ ﺑﺎ
اﺳﺘﺨﻮان ﻻﻣﻼر ﺑﺎ اﻳﺠﺎد و ﺗﻮﺳﻌﻪ ﺳﻴﺴﺘﻢ ﻫﺎورس ﺑﻪ ﺷـﻜﻞ اﺳـﺘﺨﻮان
ﺣﻀﻮر ﺗﻌﺪاد ﻓﺮاواﻧﻲ از ﻓﻴﺒﺮوﺑﻼﺳﺖﻫﺎ و رﺷﺘﻪﻫﺎي ﻛـﻼژن ﻣـﺸﺨﺺ
ﻣﺘﺮاﻛﻢ ﻛﻮرﺗﻴﻜﺎل ﭘﺮ ﺷﺪه اﺳـﺖ و اﻓﺰاﻳـﺶ ﻗﺎﺑـﻞ ﺗﻮﺟﻬـﻲ در ﺗﺸﻜﻴـﻞ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻏﻔﻮر ﻣﻮﺳﻮي و ﻫﻤﻜﺎران
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ﺷﻜﻞ :1 -ﻧﻤﺎي رﻳﺰﺑﻴﻨﻲ از ﺟﺎﻳﮕﺎه ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ
ﺷﻜﻞ :3 -ﻧﻤﺎي رﻳﺰﺑﻴﻨﻲ از ﺟﺎﻳﮕﺎه ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ
ﻓﻤﻮر ﻳﻚ ﻣﻮش ﺻﺤﺮاﻳﻲ ﮔﺮوه ﺷﺎﻫﺪ -A .ﺑﻪ اﺳﭙﻴﻜﻮلﻫﺎي اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﺗﺎزه ﺗﺸﻜﻴﻞ و
ﻓﻤﻮر ﻳﻚ ﻣﻮش ﺻﺤﺮاﻳﻲ از ﮔﺮوه ﺗﻴﻤﺎر ﺑﺎ دوز -A .20mg/kgﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ
ﻓﻀﺎﻫﺎي وﺳﻴﻊ ﻣﻐﺰ اﺳﺘﺨﻮاﻧﻲ ﻣﺎﺑﻴﻦ آنﻫﺎ ﻛﻪ ﻗﺴﻤﺖ اﻋﻈﻢ ﻧﻘﻴﺼﻪ )ﻓﻀﺎي ﺑﻴﻦ دو ﭘﻴﻜﺎن( را ﭘﺮ
ﺗﻘﺮﻳﺒﺎَ ﺑﻪﻃﻮر ﻛﺎﻣﻞ ﺗﻮﺳﻂ اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ ﭘﺮ ﺷﺪه اﺳﺖ )ﻓﻀﺎي ﺑﻴﻦ دو ﭘﻴﻜﺎن( .ﻓﻀﺎﻫﺎي
ﻛﺮده ﺗﻮﺟﻪ ﻓﺮﻣﺎﻳﻴﺪ) .ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ -B ،(×100اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﻗﺴﻤﺖ
ﻣﻐﺰ اﺳﺘﺨﻮاﻧﻲ ﻣﺎﺑﻴﻦ ﺗﻴﻐﻪﻫﺎي اﺳﺘﺨﻮاﻧﻲ ﻣﺘﺮاﻛﻢ اوﻟﻴﻪ ﺑﻪ ﺷﺪت ﻛﺎﻫﺶ ﻳﺎﻓﺘﻪ و ﻣﻘﺪار اﺳﺘﺨﻮان ﺗﺎزه
اﻋﻈﻢ ﻧﺴﺞ ﺗﺮﻣﻴﻤﻲ را در ﻣﺤﻞ ﻧﻘﻴﺼﻪ ﺑﻪ ﺧﻮد اﺧﺘﺼﺎص داده اﺳﺖ .اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﺗﺎزه ﺗﺸﻜﻴﻞ
ﺗﺸﻜﻴﻞ ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺗﻴﻤﺎر ﺑﺎ دوز 10ﻣﻴﻠﻲﮔﺮم ﺑﻴﺶﺗﺮ ﻣﻲﺑﺎﺷﺪ .اﻓﺰاﻳﺶ ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ در
در ﻣﺤﻞ ارﺗﻔﺎق ﺑﺎ اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ ﻣﺠﺎور ﻧﻘﻴﺼﻪ ،در ﺣﺎل ﺟﺎﻳﮕﺰﻳﻨﻲ ﺑﺎ اﺳﺘﺨﻮان ﺗﻴﻐﻪاي اوﻟﻴﻪ
ﺗﺸﻜﻴﻞ اﺳﺘﺨﻮان ﻧﻮﺑﻨﻴﺎد ﻣﺸﺎﻫﺪه ﻣﻲﺷﻮد .ﭘﻴﻮﺳﺘﮕﻲ ﺑﻴﻦ اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ و اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ
ﻣﻲﺑﺎﺷﺪ )ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ .(×400
ﻫﻢﭼﻨﺎن ﺑﺮﻗﺮار ﻣﻲﺑﺎﺷﺪ )ﻣﺤﻞ ﭘﻴﻜﺎن( )ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ -B .(×250اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ ﺑﺎ اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ )ﺳﺘﺎره( ﭘﻴﻮﺳﺘﻪ و ﻣﺪاوم ﺑﻮده و اﻓﺰاﻳﺶ ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ در رﻳﻤﻮدﻟﻴﻨﮓ ﺑﺎﻓﺖ اﺳﺘﺨﻮاﻧﻲ ﺗﺎزه ﺗﺸﻜﻴﻞ و ﺗﻮﺳﻌﻪ ﺳﻴﺴﺘﻢﻫﺎي ﻫﺎورﺳﻲ )ﭘﻴﻜﺎنﻫﺎي ﻧﺎزك( در اﻳﻦ ﻧﻤﻮﻧﻪ ﻣﺸﺨﺺ ﻣﻲﺑﺎﺷﺪ .ﺳﻄﺢ ﻣﺸﺘﺮك ﻣﺸﺨﺼﻲ )ﭘﻴﻜﺎن ﺿﺨﻴﻢ( ﺑﻴﻦ اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ ﻣﺘﺮاﻛﻢ و اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ ﻗﺎﺑﻞ ﻣﺸﺎﻫﺪه ﻣﻲﺑﺎﺷﺪ )ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ .(×400
اﺳﺘﺨﻮان ﻧﻮﺑﻨﻴﺎد ﻣـﺸﺎﻫﺪه ﻣـﻲﺷـﻮد .ﭘﻴﻮﺳـﺘﮕﻲ ﻣـﺎﺑﻴﻦ اﺳـﺘﺨﻮان ﺗـﺎزه ﺗﺸﻜﻴﻞ و اﺳﺘﺨﻮان ﻗﺪﻳﻤﻲ ﺑﻪوﺟﻮد آﻣﺪه اﺳﺖ )ﺷﻜﻞ .(3 ﻳﺎﻓﺘﻪﻫﺎي ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي :ارزﻳﺎﺑﻲ ﻧﺘـﺎﻳﺞ ﻫﻴـﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺑـﻪ دﺳﺖ آﻣﺪه ،ﻧﺸﺎندﻫﻨﺪه آن اﺳﺖ ﻛـﻪ ﻣﻘـﺎدﻳﺮ اﺳـﺘﺨﻮان ﻻﻣـﻼر ﺷـﻜﻞ ﮔﺮﻓﺘﻪ در ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ دوم و ﺳﻮم ﺑﻪ ﻃﻮر ﻣﻌﻨﻲداري ﺑﻴﺶﺗـﺮ از ﮔﺮوه ﺷﺎﻫﺪ و ﻛﻢﺗﺮ از اﺳﺘﺨﻮان ﺳﺎﻟﻢ ﻣﻲﺑﺎﺷﺪ ) .(P<0/0001ﺑﻴﺶﺗﺮﻳﻦ ﻣﻘﺪار اﺳﺘﺨﻮان ﻻﻣﻼر ﺷﻜﻞ ﮔﺮﻓﺘﻪ ﺑﻴﻦ ﮔـﺮوهﻫـﺎي ﻣـﻮرد ﻣﻄﺎﻟﻌـﻪ ،در ﮔﺮوه آزﻣﺎﻳﺶ ﺳﻮم )آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﺑﺎﻻ( ﻣﻲﺑﺎﺷﺪ .ﻣﻘﺪار اﺳﺘﺨﻮان ﺷﻜﻞ :2 -ﻧﻤﺎي رﻳﺰﺑﻴﻨﻲ از ﺟﺎﻳﮕﺎه ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ ﻓﻤﻮر ﻳﻚ ﻣﻮش ﺻﺤﺮاﻳﻲ از ﮔﺮوه ﺗﻴﻤﺎر ﺑﺎ دوز .10mg/kg
ﻧﺎﺑﺎﻟﻎ و ﻣﻐﺰ اﺳﺘﺨﻮان در ﮔﺮوه ﺷﺎﻫﺪ ﺑـﻪﻃـﻮر ﻣﻌﻨـﻲداري ﺑـﻴﺶﺗـﺮ از ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ دوم و ﺳﻮم ﻣﻲﺑﺎﺷﺪ ) .(P<0/0001در ﻣﻘﺎﻳﺴﻪ دو ﺑﻪ
-Aﺗﻮده ﺑﺎرﻳﻜﻲ ﻣﺘﺸﻜﻞ از اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ و اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ اوﻟﻴﻪ ﺗﺎزه ﺗﺸﻜﻴﻞ ،ﻓﻀﺎي ﻧﻘﻴﺼﻪ
دو ﻣﺎﺑﻴﻦ ﮔﺮوهﻫﺎي ﻣـﻮرد ﻣﻄﺎﻟﻌـﻪ از ﻟﺤـﺎظ ﻣﻴـﺰان ﺗـﺸﻜﻴﻞ اﺳـﺘﺨﻮان
)ﻓﻀﺎي ﺑﻴﻦ دوﭘﻴﻜﺎن( را ﺗﺎ ﺣﺪودي اﺷﻐﺎل ﻧﻤﻮده و ﻧﻘﻴﺼﻪ را ﻣﺴﺪود ﻧﻤﻮده اﺳﺖ
ﻻﻣﻼر ﺗﻔﺎوت ﻣﻌﻨﻲداري ﺑﻴﻦ ﮔﺮوه آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﭘﺎﻳﻴﻦ و ﮔـﺮوه
)ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ -B .(×250ﻓﻀﺎﻫﺎي ﻣﻐﺰ اﺳﺘﺨﻮاﻧﻲ ﻣﺎﺑﻴﻦ ﺗﻴﻐﻪﻫﺎي ﻧﺎﺑﺎﻟﻎ و ﻣﺘﺮاﻛﻢ اوﻟﻴﻪ ﺗﺎزه ﺗﺸﻜﻴﻞ ﻫﻢﭼﻨﺎن ﺑﺎﻗﻲ ﺑﻮده ،ﻟﻜﻦ ﺑﺎﻓﺖ اﺳﺘﺨﻮان ﺗﺎزه ﺗﺸﻜﻴﻞ از ﺗﺮاﻛﻢ ﻧﺴﺒﺘﺎَ
ﺷﺎﻫﺪ وﺟﻮد دارد ﻫﻢﭼﻨﻴﻦ ﻣـﺎﺑﻴﻦ ﮔـﺮوه آﺗﻮرواﺳـﺘﺎﺗﻴﻦ ﺑـﺎ دوز ﺑـﺎﻻ و
ﺑﻴﺶﺗﺮي ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺷﺎﻫﺪ ﺑﺮﺧﻮردار ﻣﻲﺑﺎﺷﺪ )ﻫﻤﺎﺗﻮﻛﺴﻴﻠﻴﻦ -اﺋﻮزﻳﻦ ،ﺑﺰرگﻧﻤﺎﻳﻲ .(×400
ﮔﺮوه ﺷﺎﻫﺪ ﻧﻴﺰ ﺗﻔﺎوت ﻣﻌﻨﻲدار ﻣﻲﺑﺎﺷـﺪ ) (P<0/0001و ﻧﻴـﺰ ﺗﻔـﺎوت
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺗﺎﺛﻴﺮ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در ران ﻣﻮش
82
ﺟﺪول :1 -ﻣﻘﺎﻳﺴﻪ ﻣﻴﺎﻧﮕﻴﻦ و اﻧﺤﺮاف اﺳﺘﺎﻧﺪارد اﺟﺰاي ﺑﺎﻓﺖ اﺳﺘﺨﻮان ﺟﺎﻳﮕﺎه ﺗﺮﻣﻴﻢ ﺑﻴﻦ ﮔﺮوهﻫﺎي ﻣﻮرد ﻣﻄﺎﻟﻌﻪ )ﺗﻌﺪاد ﻣﻮشﻫﺎي ﻣﻮرد ﻣﻄﺎﻟﻌﻪ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي در ﻫﺮ ﮔﺮوه 10ﺳﺮ ﻣﻲﺑﺎﺷﺪ(.
اﺟﺰاي ﺑﺎﻓﺖ اﺳﺘﺨﻮان
اﺳﺘﺨﻮان ﺳﺎﻟﻢ
اﺳﺘﺨﻮان ﻻﻣﻼر
95/10±1/59a
ﮔﺮوه اول )ﺷﺎﻫﺪ(
اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﻣﻐﺰ اﺳﺘﺨﻮان
a a
4/20±1/31 0/80±0/63
ﮔﺮوه دوم )آﺗﻮرواﺳﺘﺎﺗﻴﻦ (10mg/kg
13/10±2/02b
c
b
c
b
37/20±2/25 49/70±2/86
c
42/30±1/41 29/20±1/22 28/60±1/17
ﮔﺮوه ﺳﻮم )آﺗﻮرواﺳﺘﺎﺗﻴﻦ (20mg/kg d d d
55/90±2/55 21/30±1/41 22/80±1/31
:a b cﺣﺮوف ﻏﻴﺮ ﻣﺸﺎﺑﻪ ﻧﺸﺎندﻫﻨﺪه ﻣﻌﻨﻲدار ﺑﻮدن اﺧﺘﻼف در ﻫﺮ ردﻳﻒ ﻣﻲﺑﺎﺷﺪ .ﻣﻘﺎدﻳﺮ اﺳﺘﺨﻮان ﻻﻣﻼر ﺷﻜﻞ ﮔﺮﻓﺘﻪ در ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ دوم و ﺳـﻮم ﺑـﻴﺶﺗـﺮ از ﮔـﺮوه ﺷـﺎﻫﺪ ) .(P<0/0001ﺗﻔـﺎوت ﻣﻌﻨﻲداري ﺑﻴﻦ دو ﮔﺮوه آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﺑﺎﻻ و ﭘﺎﻳﻴﻦ از ﻟﺤﺎظ ﻣﻴﺰان ﺗﺸﻜﻴﻞ اﺳﺘﺨﻮان ﻻﻣﻼر ﻣﺸﺎﻫﺪه ﻣﻲﺷﻮد ).(P<0/0001
ﻣﻌﻨﻲداري ﺑﻴﻦ دو ﮔﺮوه آﺗﻮرواﺳـﺘﺎﺗﻴﻦ ﺑـﺎ دوز ﺑـﺎﻻ و ﭘـﺎﻳﻴﻦ از ﻟﺤـﺎظ
ﺗﺸﻜﻴﻞ ﺷﺪه ﺑﻮدﻧﺪ .در ﮔﺮوه ﺗﻴﻤﺎر ﺑﺎ آﺗﻮرواﺳـﺘﺎﺗﻴﻦ ﺑـﺎ دوز 10mg/kg
ﻣﻴﺰان ﺗﺸﻜﻴﻞ اﺳﺘﺨﻮان ﻻﻣﻼر ﻣـﺸﺎﻫﺪه ﻣـﻲﺷـﻮد ) .(P<0/0001ﻧﺘـﺎﻳﺞ
ﺗﻨﻬﺎ ﻻﻳﻪ ﻧﺎزﻛﻲ از اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ و ﻣﺘﺮاﻛﻢ اوﻟﻴﻪ ﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ را ﭘﺮ
ارزﻳﺎﺑﻲ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺗﺮﻣﻴﻢ و ﻣﻘﺎﻳﺴﻪ آن ﻣﺎﺑﻴﻦ ﮔـﺮوهﻫـﺎي ﻣـﻮرد
ﻛﺮده ﺑﻮد ،اﻳﻦ در ﺣﺎﻟﻲ اﺳﺖ ﻛﻪ ﺑﺎ اﻓﺰاﻳﺶ دوز دارو ﺑﻪ 20mgﻧﻘﻴـﺼﻪ
آزﻣﺎﻳﺶ ،در ﺟﺪول 1اراﻳﻪ ﮔﺮدﻳﺪه اﺳﺖ.
اﺳﺘﺨﻮاﻧﻲ ﺑﻪ ﺻﻮرت ﺗﻘﺮﻳﺒﺎ ﻛﺎﻣﻞ ﺑﺎ اﺳـﺘﺨﻮان ﺟﺪﻳـﺪ ﻣﺘـﺮاﻛﻢ ﺷـﺪه و ﺳﺎزﻣﺎن ﻳﺎﻓﺘﻪ ﻣﺴﺪود ﮔﺮدﻳﺪه ﺑﻮد ﻻﻳﻪﻫﺎي اﺳﺘﺨﻮاﻧﻲ ﺑﻪ ﻫﻢ ﻓـﺸﺮدهﺗـﺮ
ﺑﺤﺚ
ﮔﺸﺘﻪ و ﺳﻴﺴﺘﻢ ﻫﺎورس در ﺣﺎل ﺷﻜﻞﮔﻴﺮي ﺑﻮد و ﻣﻘـﺎدﻳﺮ ﻣﺨﺘﻠﻔـﻲ از اﺳﺘﺨﻮان دﻳﺪه ﻣﻲﺷﺪ ﻛﻪ ﻧﺎﺣﻴﻪ ﺗﺮﻣﻴﻢ را ﭘﺮ ﻛﺮده ﺑﻮد .ﺑﻪ ﻃﻮري ﻛﻪ ﭘﺲ
در ﺑﺮرﺳــﻲ ﺣﺎﺿــﺮ ،ﻧﺘــﺎﻳﺞ رﻳﺰﺑﻴﻨــﻲ ﺳــﺎﺧﺘﺎر ﺗــﺮﻣﻴﻢ ﺣﻜﺎﻳــﺖ از
از ﮔﺬﺷﺖ 45روز ﻣﻘﺎدﻳﺮي از ﺗﺮاﺑﻜﻮلﻫـﺎي اﺳـﺘﺨﻮاﻧﻲ ﻧـﺴﺒﺘﺎً ﺑـﺎﻟﻎ و
اﺳﺘﺨﻮانﺳﺎزي داﺧﻞ ﻏﺸﺎﻳﻲ در ﻧﻘﻴﺼﻪ اﻳﺠﺎد ﺷﺪه در اﺳﺘﺨﻮان ﻣﺘﺮاﻛﻢ
ﻣﻨﻈﻢ و در ﺣﺎل ﺗﺒﺪﻳﻞ ﺷﺪن ﺑﻪ اﺳﺘﺨﻮان از ﻧﻮع ﻻﻣﻼر ﻧﺎﺣﻴﻪ ﺗـﺮﻣﻴﻢ را
ران ﻣﻮشﻫﺎي ﺻﺤﺮاﻳﻲ دارد .در اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﺗﺠﺮﺑـﻲ ﺑـﻪ دﻟﻴـﻞ آنﻛـﻪ
ﭘﺮ ﻛﺮده ﺑﻮد ﻛﻪ ﻧﺘﺎﻳﺞ ﺑﻪدﺳﺖ آﻣﺪه از ﻣﻄﺎﻟﻌﺎت ﻗﺒﻠﻲ را ﻣﻮرد ﺗﺎﻳﻴﺪ ﻗﺮار
ﻛﺎﻧﺎل اﻳﺠﺎد ﺷﺪه داراي ﻗﻄﺮ ﻣﺤﺪودي ﺑﻮد ،اﻟﺘﻴﺎم ﺗﻨﻬـﺎ ﺑـﺎ ﻓﻌـﺎل ﺷـﺪن
ﻣﻲدﻫﺪ و ﺑﻪ ﺗﺎﺛﻴﺮ ﻣﺜﺒﺖ آﺗﻮرواﺳﺘﺎﺗﻴﻦ در روﻧﺪ اﺳﺘﺨﻮانﺳـﺎزي دﻻﻟـﺖ
ﺳﻠﻮلﻫـﺎي اﺳـﺘﺌﻮﭘﺮوژﻧﻴﺘﻮر آﻧﺪوﺳـﺘﻲ ﻛـﻪ ﻗﺎﺑﻠﻴـﺖ ﺗﺒـﺪﻳﻞ ﺷـﺪن ﺑـﻪ
ﻣﻲﻧﻤﺎﻳﺪ .ﻣﻘﺎﻳﺴﻪ ﻛﻴﻔﻲ ﻧﺘﺎﻳﺞ ﺑﻴﻦ دو ﮔـﺮوه ﻧـﺸﺎندﻫﻨـﺪه ﺗـﺎﺛﻴﺮ ﻣﺜﺒـﺖ
اﺳﺘﺌﻮﺑﻼﺳﺖﻫﺎ را دارﻧﺪ ،ﺻﻮرت ﮔﺮﻓﺘﻪ اﺳﺖ .ﺑﺎ ﺷﻜﻞﮔﻴﺮي اﺳـﺘﺨﻮان
آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﺑﺎﻻ ﻧﺴﺒﺖ ﺑﻪ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﭘﺎﻳﻴﻦ ﻣﻲﺑﺎﺷـﺪ
ﻧﺎﻣﻨﻈﻢ و ﻧﺎﺑﺎﻟﻎ و ﺑﺎ ﮔﺬﺷﺖ زﻣﺎن ﺗﻐﻴﻴﺮاﺗﻲ در اﺳﭙﻴﻜﻮلﻫـﺎي اﺳـﺘﺨﻮان
و ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ ﻛﻪ ﺗﺎﺛﻴﺮ اﻳﻦ دارو واﺑﺴﺘﻪ ﺑﻪ دوز ﻣـﻲﺑﺎﺷـﺪ .ارزﻳـﺎﺑﻲ
ﻧﺎﺑﺎﻟﻎ ﭘﺪﻳﺪ آﻣـﺪه و ﺑـﺎ ﻣـﻨﻈﻢ ﺷـﺪن رﺷـﺘﻪﻫـﺎي ﻛـﻼژن در آنﻫـﺎ ﺑـﻪ
ﻧﺘﺎﻳﺞ ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﻧﻴﺰ ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ ﻗﺴﻤﺖ اﻋﻈـﻢ ﻧﻘﻴـﺼﻪ در
اﺳﺘﺨﻮانﻫﺎي ﻣﻨﻈﻢ ﺑﺎﻟﻎ ﺗﺒﺪﻳﻞ ﺷﺪه ﺑﻮدﻧﺪ ﻣﺴﻠﻢ اﺳﺖ ﻛﻪ ﺑﻪ اﻳـﻦ ﻧـﻮع
ﮔﺮوه ﺷﺎﻫﺪ ﺗﻮﺳﻂ اﺳﺘﺨﻮان ﻧﺎﺑـﺎﻟﻎ و ﻓـﻀﺎﻫﺎي وﺳـﻴﻊ ﻣﻐـﺰ اﺳـﺘﺨﻮان
اﺳﺘﺨﻮانﺳﺎزي ،درون ﻏﺸﺎﻳﻲ اﻃﻼق ﻣﻲﮔﺮدد14.و 13در ﮔﺮوه ﺷﺎﻫﺪ ﻛـﻪ
ﻣﺎﺑﻴﻦ آن ﭘﺮ ﺷﺪه اﺳﺖ .اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ و ﻓﻀﺎي ﻣﻐﺰ اﺳﺘﺨﻮان ﺑـﻪﻃـﻮر
ﭘﺲ از اﻳﺠﺎد ﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ درﻣﺎن داروﻳﻲ اﻧﺠﺎم ﻧﺸﺪه ﺑـﻮد ،ﺗﺒـﺪﻳﻞ
ﻣﻌﻨﻲداري ﺑﻴﺶﺗﺮ از ﮔﺮوهﻫﺎي آزﻣﺎﻳﺶ دوم و ﺳﻮم ﻣﻲﺑﺎﺷـﺪ و ﻣﻘـﺪار
ﺑﺎﻓﺖ ﻫﻤﺒﻨﺪي ﺑﻪ اﺳﺘﺨﻮان و ﺷﻜﻞﮔﻴـﺮي اﻟﺘﻴـﺎم از وﺳـﻌﺖ و ﻛﻴﻔﻴـﺖ
اﺳﺘﺨﻮان ﻻﻣﻼر ﺗﺸﻜﻴﻞ ﺷﺪه در ﮔﺮوه ﺷﺎﻫﺪ ﺑﺴﻴﺎر ﻛﻢ ﻣﻲﺑﺎﺷﺪ ،اﻳﻦ در
ﺑﺎﻻﻳﻲ ﺑﺮﺧﻮردار ﻧﺒﻮد و ﭘﺲ از ﮔﺬﺷـﺖ 45روز ﺗﻨﻬـﺎ ﻻﻳـﻪ ﻧـﺎزﻛﻲ از
ﺣﺎﻟﻲ اﺳﺖ ﻛﻪ در ﮔـﺮوهﻫـﺎي آزﻣـﺎﻳﺶ دوم و ﺳـﻮم ﻣﻘـﺪار اﺳـﺘﺨﻮان
اﺳﺘﺨﻮان ﻧﺎﺑﺎﻟﻎ ﻛﻪ ﻓﻀﺎﻫﺎي وﺳﻴﻌﻲ از ﻣﻐﺰ اﺳـﺘﺨﻮان در ﺑـﻴﻦ آن دﻳـﺪه
ﻻﻣﻼر ﺑﻪ ﻃﻮر ﻣﻌﻨﻲداري ﺑﻴﺶﺗﺮ از ﮔﺮوه ﺷﺎﻫﺪ اﺳﺖ .ﻣﻘﺎﻳﺴﻪ ﺑـﻴﻦ دو
ﻣﻲﺷﺪ ﺗﺸﻜﻴﻞ ﺷﺪه ﺑﻮد .ﭼﻨﺎنﭼﻪ از ﻧﺘﺎﻳﺞ ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي ﺑﺮ ﻣـﻲآﻳـﺪ
ﮔﺮوه درﻳﺎﻓﺖ ﻛﻨﻨﺪه آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺎ دوز ﺑﺎﻻ و ﭘﺎﻳﻴﻦ ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛـﻪ
در ﮔﺮوهﻫﺎي ﺗﻴﻤﺎر ﺑﺎ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﻌﺪ از ﮔﺬﺷﺖ 45روز از ﺟﺮاﺣـﻲ
ﺑﺎ اﻓﺰاﻳﺶ دوز دارو ،ﺑﺮ ﻣﻘﺪار اﺳﺘﺨﻮان ﻻﻣﻼر ﻧﻴﺰ ﺑﻪ ﻃـﻮر ﻣﻌﻨـﻲداري
ﺗﻴﻐﻪﻫﺎي اﺳﺘﺨﻮاﻧﻲ ﺳﺎزﻣﺎن ﻳﺎﻓﺘﻪ و ﻣـﻨﻈﻢﺗـﺮ ﻧـﺴﺒﺖ ﺑـﻪ ﮔـﺮوه ﺷـﺎﻫﺪ
اﻓﺰوده ﺷﺪه اﺳﺖ ﻛﻪ ﻧـﺸﺎندﻫﻨـﺪه اﺳـﺘﺨﻮانﺳـﺎزي ﻓﻌـﺎل ﻧـﺴﺒﺖ ﺑـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻫﻤﻜﺎران ﻣﻮﺳﻮي و Mousavi ﻏﻔﻮرGh. et al.
83
ﮔﺮوهﻫﺎي دﻳﮕﺮ ﻣﻲﺑﺎﺷﺪ ،وﻟﻲ ﺑﺎ اﻳﻦ ﺣـﺎل ﻣﻘـﺪار اﺳـﺘﺨﻮان ﻻﻣـﻼر از
اﺳﺘﻔﺎده ﺷﻮد ) (1mg/kg/dayﺗﺸﻜﻴﻞ اﺳﺘﺨﻮان ﻛـﺎﻫﺶ ﻣـﻲﻳﺎﺑـﺪ 20.در
ﻣﻘﺪار ﻃﺒﻴﻌﻲ آن در اﺳﺘﺨﻮان ﺳـﺎﻟﻢ ﻛـﻢﺗـﺮ ﻣـﻲﺑﺎﺷـﺪ .ارزﻳـﺎﺑﻲ ﻧﺘـﺎﻳﺞ
ﻣﻄﺎﻟﻌــﻪ Kawaneﻣــﺸﺨﺺ ﺷــﺪه اﺳــﺖ ﻛــﻪ داﻧــﺴﻴﺘﻪ اﺳــﺘﺨﻮان در
ﻫﻴﺴﺘﻮﭘﺎﺗﻮﻟﻮژي و ﻫﻴﺴﺘﻮﻣﻮرﻓﻮﻣﺘﺮي ﺑـﻪ دﺳـﺖ آﻣـﺪه در اﻳـﻦ ﺗﺤﻘﻴـﻖ
ﻣﻮشﻫﺎي ﺻﺤﺮاﻳﻲ ﻛﻪ رﺣﻢ و ﺗﺨﻤﺪانﻫﺎي آنﻫﺎ ﺑﺮداﺷـﺘﻪ ﺷـﺪه ﺑـﻮد،
ﻧﺸﺎندﻫﻨﺪة آن اﺳـﺖ ﻛـﻪ داروي آﺗﻮرواﺳـﺘﺎﺗﻴﻦ ﺑﺎﻋـﺚ ﺗـﺴﺮﻳﻊ روﻧـﺪ
22
ﻣﺘﻌﺎﻗﺐ ﺗﻴﻤﺎر ﺑﺎ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﻪ ﻃﻮر ﻣﻌﻨﻲداري اﻓﺰاﻳﺶ ﭘﻴﺪا ﻣﻲﻛﻨﺪ.
اﺳﺘﺨﻮان ﺳﺎزي ﻣﻲ ﺷﻮد Mundy .ﻧﺸﺎن داد ﻛﻪ اﺳـﺘﺎﺗﻴﻦﻫـﺎ ﺑـﺎ اﻓـﺰاﻳﺶ
در راﺑﻄــﻪ ﺑــﺎ ﻓﺎرﻣﺎﻛﻮﻛﻴﻨﺘﻴــﻚ ،ﻣﺤﻘﻘــﺎن ﻣﻼﺣﻈــﻪ ﻛــﺮدهاﻧــﺪ ﻛــﻪ دوز
BMP-2ﺑﺎﻋﺚ اﻓﺰاﻳﺶ ﻓﻌﺎﻟﻴﺖ اﺳﺘﺌﻮﺑﻼﺳـﺖﻫـﺎ ﺷـﺪه و از اﻳـﻦ ﻃﺮﻳـﻖ
10mg/kg/dayﺑﺮاي ﻣﻮش ﺻﺤﺮاﻳﻲ ﻣﻌﺎدل 70mg/kg/dayﺑﺮاي اﻧﺴﺎن
Wong
اﺳﺖ .ﻣﺤﺎﺳﺒﻪﻫﺎ اﻳﻦ ﻃﻮر ﻧﺸﺎن دادهاﻧـﺪ ﻛـﻪ ﻓﺮآﻳﻨـﺪﻫﺎي ﻣﺘﺎﺑﻮﻟﻴـﻚ در
ﺣﺠﻢ اﺳﺘﺨﻮاﻧﻲ را اﻓﺰاﻳﺶ ﻣﻲدﻫﻨﺪ 5.در ﻣﻄﺎﻟﻌﻪاي ﻛـﻪ ﺗﻮﺳـﻂ
21
اﻧﺠﺎم ﺷﺪه اﺳﺖ ،ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ ﺗﺮﻛﻴﺐ ﻛﻼژن و اﺳﺘﺎﺗﻴﻦ ﻳـﻚ ﻣـﺎده
ﺟﻮﻧﺪﮔﺎن 10ﻣﺮﺗﺒﻪ ﻧﺴﺒﺖ ﺑﻪ اﻧﺴﺎن ﺳﺮﻳﻊﺗﺮ اﻧﺠﺎم ﻣﻲﮔﻴﺮد.
اﺳﺘﺌﻮاﻳﻨﺪاﻛﺘﻴﻮ اﺳﺖ و زﻣـﺎﻧﻲ ﻛـﻪ در ﺷﻜـﺴﺘﮕﻲﻫـﺎي ﺟﻤﺠﻤـﻪ ﻣـﻮرد
ﭘﺲ از ﺟﺬب ﮔﻮارﺷﻲ %95 ،اﺳﺘﺎﺗﻴﻦ در ﻛﺒﺪ ﻣﺘـﺎﺑﻮﻟﻴﺰه ﻣـﻲﺷـﻮد،
اﺳﺘﻔﺎده ﻗﺮار ﻣﻲﮔﻴﺮد ﺑﺎ اﺳﺘﺨﻮان ﺑـﻪ راﺣﺘـﻲ ﭘﻴﻮﻧـﺪ ﻣـﻲﻳﺎﺑـﺪ و ﺑﺎﻋـﺚ
ﺗﻨﻬﺎ ﺑﺨﺶ ﻛﻮﭼﻜﻲ از آن از ﻃﺮﻳﻖ ﻛﺒﺪ ﻋﺒﻮر ﻣﻲﻛﻨﺪ و ﺑـﻪ ﺳـﻠﻮلﻫـﺎي
Wong
اﺳﺘﺨﻮان ﻣﻲرﺳﺪ .ﺑﻨﺎﺑﺮاﻳﻦ داروﻫﺎي اﺳﺘﺎﺗﻴﻨﻲ ﻛـﻪ ﻫـﻢ اﻛﻨـﻮن ﺑـﻪﻃـﻮر
BMP
ﺗﺠﺎري در دﺳﺘﺮس ﻗﺮار ﻣﻲﮔﻴﺮﻧﺪ ،ﻛﺒﺪ را ﻫﺪف ﻗﺮار ﻣﻲدﻫﻨﺪ و ﺑـﺮاي
ﺗﺴﺮﻳﻊ در زﻣﺎن اﻟﺘﻴﺎم ﻣﻲﮔﺮدد 15.در ﻣﻄﺎﻟﻌﻪ دﻳﮕﺮي ﻛـﻪ ﺗﻮﺳـﻂ
اﻧﺠﺎم ﺷﺪه اﺳﺖ ،اﺳـﺘﺎﺗﻴﻦ ﻣﺤﻠـﻮل در آب ﻧﻴـﺰ ﺑﺎﻋـﺚ اﻓـﺰاﻳﺶ
درﻣﺎن اﻓﺰاﻳﺶ ﻛﻠﺴﺘﺮول اﺧﺘﺼﺎص ﻳﺎﻓﺘﻨﺪ ﻧﻪ ﺳﻠﻮلﻫﺎي اﺳﺘﺨﻮاﻧﻲ.
ﻣﻲﮔﺮدد ،ﺑﻪ دﻧﺒﺎل آن اﺳﺘﺌﻮﺑﻼﺳﺖﻫﺎ و ﺗﺤﺮﻳﻚ اﺳﺘﺨﻮانﺳﺎزي اﻓﺰاﻳﺶ ﻣﻲ ﻳﺎﺑﺪ 16.در ﻣﻄﺎﻟﻌﻪ Majimaﺗـﺎﺛﻴﺮ ﻣﺜﺒـﺖ آﺗﻮرواﺳـﺘﺎﺗﻴﻦ در اﻓـﺰاﻳﺶ
ﻣﻮارد ﻓﻮق ﻃﺮاﺣﻲ اﺳﺘﺎﺗﻴﻦﻫﺎي ﺟﺪﻳﺪ را ﺑﺎ ﻫﺪفﮔﻴﺮي ﺳﻠﻮلﻫﺎي
ﺣﺠــﻢ اﺳــﺘﺨﻮاﻧﻲ در اﻓــﺮاد ﻫﻴﭙﺮﻛﻠــﺴﺘﺮوﻟﻤﻲ و ﺗــﺎﺛﻴﺮ ﻣﺜﺒــﺖ داروي
اﺳﺘﺨﻮاﻧﻲ ﭘﻴﺸﻨﻬﺎد ﻣﻲﻛﻨﺪ و ﺑﺮاي ﺗﺎﻳﻴﺪ دوز ﻣﻄﻠﻮب ﺑﺮاي ﺗﺎﺛﻴﺮ درﻣﺎﻧﻲ،
آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺑﺮ ﺗﺮﻣﻴﻢ اﺳﺘﺨﻮان در ﻣﺪت ﻛﻮﺗﺎﻫﻲ ﻧﺸﺎن داده ﺷﺪ 17.در
اﻳﺪهآل ﻧﻴﺎز ﺑﻪ ﻣﻄﺎﻟﻌﺎت زﻳﺎدي ﻣﻲﺑﺎﺷﺪ .ﻳﺎﻓﺘﻪﻫـﺎي اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ ﻧـﺸﺎن
ارزﻳﺎﺑﻲ ﺑﻴﻤﺎراﻧﻲ ﻛﻪ داروي ﺧﻮراﻛﻲ آﺗﻮرواﺳﺘﺎﺗﻴﻦ را ﺑﻪ ﻣﻨﻈﻮر درﻣـﺎن
ﻣﻲدﻫﺪ آﺗﻮرواﺳﺘﺎﺗﻴﻦ ﺳﺒﺐ اﻓﺰاﻳﺶ اﺳﺘﺨﻮانﺳﺎزي ﺷـﺪه و ﻣـﻲﺗﻮاﻧـﺪ
اﻓﺰاﻳﺶ ﻛﻠﺴﺘﺮول ﺧﻮن درﻳﺎﻓﺖ ﻛﺮده ﺑﻮدﻧﺪ ،اﻓـﺰاﻳﺶ ﻛﻤـﻲ در ﺗـﺮاﻛﻢ
اﻟﺘﻴﺎم ﻧﻘﻴﺼﻪ اﺳﺘﺨﻮاﻧﻲ را ﺗﺴﺮﻳﻊ ﻧﻤﺎﻳﺪ.
ﻣﻮاد ﻣﻌﺪﻧﻲ اﺳﺘﺨﻮان ﻧﺸﺎن داده ﺷﺪ و ﺧﻄﺮ ﺷﻜﺴﺘﮕﻲ ﻟﮕﻦ را ﻛـﺎﻫﺶ
ﺳﭙﺎﺳﮕﺰاري :اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﭘﺎﻳﺎنﻧﺎﻣﻪ ﺑﺎ ﻋﻨـﻮان "ارزﻳـﺎﺑﻲ ﺗـﺎﺛﻴﺮ
داد19.و 18ﺗﺴﺖﻫﺎي ﺣﻴﻮاﻧﻲ ﻧﺸﺎن دادهاﻧﺪ ﻛﻪ دوز ﺑـﺎﻻي ﺳﻴﻤﻮاﺳـﺘﺎﺗﻴﻦ
آﺗﻮرواﺳﺘﺎﺗﻴﻦ در ﺗﺮﻣﻴﻢ ﻧﻘﻴﺼﻪ ﺗﺠﺮﺑﻲ اﻳﺠﺎد ﺷﺪه در اﺳـﺘﺨﻮان ﻣﺘـﺮاﻛﻢ
) (20mg/kg/dayﻳﻜﻲ دﻳﮕﺮ از داروﻫﺎي اﺳﺘﺎﺗﻴﻨﻲ ،ﺗﺸﻜﻴﻞ اﺳﺘﺨﻮان را
ﻓﻤﻮر ﻣﻮش ﺻﺤﺮاﻳﻲ" در ﻣﻘﻄـﻊ دﻛﺘـﺮاي داﻣﭙﺰﺷـﻜﻲ در ﺳـﺎل 1388
اﻓﺰاﻳﺶ و ﺑﺎزﺟﺬب آن را ﻛﺎﻫﺶ ﻣـﻲدﻫـﺪ و ﻫﻨﮕـﺎﻣﻲﻛـﻪ ﺑـﺎ دوز ﻛـﻢ
ﻣﻲﺑﺎﺷﺪ و ﺑﺎ ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ ﺗﺒﺮﻳﺰ اﺟﺮا ﺷﺪه اﺳﺖ.
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Blokhuis TJ, den Boer FC, Bramer JA, van Lingen A, Roos JC, Bakker FC, et al. Evaluation of strength of healing fractures with dual energy Xray absorptiometry. Clin Orthop Relat Res 2000;(380):260-8. Hara Y, Nakamura T, Fukuda H, Harada Y, Nezu Y, Tagawa M. Changes of biomechanical characteristics of the bone in experimental tibial osteotomy model in the dog. J Vet Med Sci 2003;65(1):103-7. Kim JC, Crawford Downs J, Azuola ME, Devon Graham H 3rd. Time scale for periosteal readhesion after brow lift. Laryngoscope 2004;114(1):50-5. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003;326(7404):1423. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999;286(5446):1946-9.
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ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
Histopathologic effects of atorvastatin on experimental cortical bone defect healing in rats
12. Carmagnola D, Berglundh T, Lindhe J. The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A experimental study in labrador dogs. J Clin Periodontol 2002;29(5):377-83. 13. Liacouras PC, Owen JR, Jiranek WA, Wayne JS. Effect of pigmentation on the mechanical and polymerization characteristics of bone cement. J Arthroplasty 2006;21(4):60611. 14. Link DP, van den Dolder J, Jurgens WJ, Wolke JG, Jansen JA. Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles. Biomaterials 2006;27(28):4941-7. 15. Wong RW, Rabie AB. Statin collagen grafts used to repair defects in the parietal bone of rabbits. Br J Oral Maxillofac Surg 2003;41(4):244-8. 16. Wong RW, Rabie AB. Histologic and ultrastructural study on statin graft in rabbit skulls. J Oral Maxillofac Surg 2005;63(10):1515-21. 17. Majima T, Komatsu Y, Fukao A, Ninomiya K, Matsumura T, Nakao K. Short-term effects of atorvastatin on bone turnover in
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1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺑﺮاي2,ﭘﺎﻳﺶ روش ﻛﺎراﻳﻲ دو Tehran University Medical Journal; Vol.ﺗﺸﺨﻴﺺ 70, No. May 2012: 78-85
Histopathological and histomorphometrical effects of atorvastatin on experimental femoral cortical bone defect healing in rats
Abstract Ghafour Mousavi Ph.D.1* Daryoush Mohajeri Ph.D.2 Ali Rezaie Ph.D.1 Muhammadreza Valilu Ph.D.3 Arman Alimohamadi D.V.M.4 1- Veterinary Surgery Section, Department of Clinical Science, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran. 2- Pathology Section, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran. 3- Department of Veterinary Medicine, Shabestar Branch, Islamic Azad University, Shabestar, Iran. 4- Graduate of Veterinary Medicine, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Received: September 09, 2011 Accepted: February 04, 2012
Background: Bone remodeling has always been the goal of surgeons for a long time. Recently, it was shown that statins that are commonly prescribed for lowering cholesterol also have beneficial effects on bone healing. Therefore, the present study was undertaken to evaluate the probable effects of atorvastatin on osteogenesis in the rat femur. Methods: This experimental study was conducted on 30 male Sprague-Dawley (SD) rats. The animals were divided randomly into one control and two experiment groups. After induction of anesthesia, a hole of 2 mm in diameter was made in femur width. The control group received physiological serum but the experiment groups one and two, respectively, received 10 and 20 mg/kg/PO of atorvastatin on daily basis. After euthanizing the rats, histopathological and histomorphometrical evaluations of the bones were performed 45 days after the intervention. Results: In the control group, the defects seemed to be filled with woven bone and bone marrow, depictive of a poor osteogenic activity. In the experiment groups, many osteoblast groupings and young bone trabeculae had been formed and bone trabeculae were more organized. Histomorphometric results, showed that atorvastatin had significantly promoted bone healing in the experiment groups compared with the controls (P<0.001). Moreover, the analysis showed that atorvastatin had more significant effects in group three receiving high doses of the medication in comparison with group two (P<0.001). Conclusion: The findings of this study showed that atorvastatin is capable of stimulating osteogenesis in rats.
*
Corresponding author: Department of Clinical Science, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, East side of Pasdaran highway, Tabriz, Iran. Tel: +98- 411- 6372274 E-mail: gh_mousavi@iaut.ac.ir
Keywords: Atorvastatin, bone healing, histomorphometry, histopathology, rat.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
ﺳﺎز86-95 ،1391 اردﻳﺒﻬﺸﺖ ﺷﻤﺎرهﺑﻨﻴ،2 دوره ، ،70 ﺗﻬﺮان، داﻧﺸﮕﺎه ﻋﻠﻮم ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ، ﺎدي ﺧﻮن ﺳﻠﻮلﻫﺎي RNAiدر ﭘﺰﺷﻜﻲﻴﻚ TGF-bﺑﺎ ﺗﻜﻨ ﻣﻬﺎر ﻣﺴﻴﺮ
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ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﻪوﺳﻴﻠﻪ ﺗﻜﻨﻴﻚ RNAiدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﻛﺸﺖ داده ﺷﺪه روي دارﺑﺴﺖ ﺳﻪ ﺑﻌﺪي " DBMﻣﺎﺗﺮﻳﻜﺲ اﺳﺘﺨﻮاﻧﻲ ﻣﻌﺪﻧﻲ زداﺷﺪه"
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/09/01 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/16 :
ﭼﻜﻴﺪه
زﻫﺮااﻟﺴﺎدات ﻫﺎﺷﻤﻲ 1،ﻣﻬﺪي ﻓﺮوزﻧﺪه ﻣﻘﺪم *1،ﻣﺴﻌﻮد ﺳﻠﻴﻤﺎﻧﻲ 2،ﻣﺮﻳﻢ 4
ﺣﻔﻴﻈﻲ 3،ﻧﺎﺻﺮ اﻣﻴﺮي زاده
زﻣﻴﻨﻪ و ﻫﺪف :ﺧﻮن ﺑﻨﺪﻧﺎف در ﭘﻴﻮﻧﺪ ﻣﻐﺰ اﺳﺘﺨﻮان ،ﺑﻪﻋﻠﺖ دوز ﭘﺎﻳﻴﻦ ﺳﻠﻮلﻫﺎي CD34+داراي ﻣﺤﺪودﻳﺖﻫﺎﻳﻲ اﺳﺖ ﻛﻪ ﻣﻲﺑﺎﻳﺴﺖ اﻳﻦ ﺳﻠﻮلﻫﺎ ﻣﻮرد ﺗﺰاﻳﺪ ﻗﺮار ﮔﻴﺮﻧﺪ .ﺗﻜﺜﻴﺮ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺑﺎ اﺳﺘﻔﺎده از اﻓﺰاﻳﺶ ﻓﻌﺎﻟﻴﺖ ﺧـﻮد ﺗﻜﺜﻴـﺮي
-1ﮔﺮوه ﺑﻴﻮﺗﻜﻨﻮﻟﻮژي ﭘﺰﺷﻜﻲ ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ، داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس ،ﺗﻬﺮان ،اﻳﺮان -2ﮔﺮوه ﻫﻤﺎﺗﻮﻟﻮژي و ﺑﺎﻧﻚ ﺧﻮن ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس ،ﺗﻬﺮان ،اﻳﺮان
آنﻫﺎ در ﺷﺮاﻳﻂ آزﻣﺎﻳﺸﮕﺎﻫﻲ روي دارﺑﺴﺖ ) DBMﻣﺎﺗﺮﻳﻜﺲ اﺳﺘﺨﻮاﻧﻲ ﻣﻌﺪﻧﻲزدا ﺷﺪه( ﭘﻮﺷﻴﺪه ﺷـﺪه ﺑـﺎ ﺳـﻠﻮلﻫـﺎي ﭘﺮوژﻧﻴﺘﻮر ﻣﺰاﻧﺸﻴﻤﻲ ﻳﻌﻨﻲ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺳﻮﻣﺎﺗﻴﻚ ﻏﻴﺮ ﻣﺤﺪود ﺷـﺪه ) (USSCﭘﻴـﺸﻨﻬﺎد ﻣـﻲﺷـﻮد .ﻣـﺴﻴﺮ TGF-bاز ﻋﻮاﻣﻞ ﻣﻬﻢ ﻣﻬﺎري ﺑﺮاي ﻓﻌﺎﻟﻴﺖ ﺧﻮد ﺗﺠﺪﻳﺪ ﺷﻮﻧﺪﮔﻲ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي اﺳﺖ ﻛﻪ در اﻳﻦ ﺗﺤﻘﻴﻖ از ﻫـﻢزﻣـﺎﻧﻲ ﻛـﺸﺖ )vivo
(Exو ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﺎ ﻛﻤﻚ ﺗﻜﻨﻴﻚ RNAiاﺳﺘﻔﺎده ﺷﺪ .روش ﺑﺮرﺳﻲ :ﺳﻠﻮلﻫﺎي ،USSCاز ﺧﻮن
-3ﮔﺮوه ﺑﻴﻮﻟﻮژي ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ،ﻣﺮﻛﺰ
ﺑﺮون ﺗﻦ
ﺗﺤﻘﻴﻘﺎت ﻓﻨﺎوري ﺑﻦﻳﺎﺧﺘﻪ ،ﺗﻬﺮان ،اﻳﺮان
ﺑﻨﺪﻧﺎف ﺟﺪا ﺷﺪه و ﺳﭙﺲ روي دارﺑﺴﺖ DBMو ﻫﻢ ﻛﻒ ﭘﻠﻴﺖ ،ﺑﻪ ﻋﻨﻮان ﻻﻳﻪ ﻣﻐﺬي ،ﭘﻮﺷﺶ داده ﺷﺪﻧﺪ .ﺳـﻠﻮلﻫـﺎي
-4ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﺳﺎزﻣﺎن اﻧﺘﻘﺎل ﺧﻮن ،ﺗﻬﺮان،
CD34+ﺑﺎ روش ) Magnetic-Activated Cell Sorting (MACSاز ﺟﻔﺖ اﻧﺴﺎﻧﻲ ﺗﺨﻠـﻴﺺ و در ﺷـﺮاﻳﻂ دو ﺑﻌـﺪي و ﺳـﻪ
اﻳﺮان
ﺑﻌﺪي ﻫﻢ ﻛﺸﺘﻲ ،ﺑﺎ siRNAﻋﻠﻴﻪ TGFbR2ﺗﻴﻤﺎر ﺷﺪﻧﺪ .ﻣﻴﺰان ﺳﺮﻛﻮب ﺑﻴﺎن ژن ﻣﺮﺑﻮﻃﻪ ﺑﺎ Real-Time PCRﻛﻤﻲ ﺑﺮرﺳﻲ
ﺷﺪﻧﺪ .در ﻧﻬﺎﻳﺖ ﺷﻤﺎرش ﺳﻠﻮﻟﻲ ،ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي و ﻓﻌﺎﻟﻴﺖ ﻛﻠﻨﻲزاﻳﻲ ﺳﻠﻮلﻫﺎ ﻣﻮرد ارزﻳـﺎﺑﻲ ﻗـﺮار ﮔﺮﻓـﺖ .ﻳﺎﻓﺘـﻪﻫـﺎ: ﻛﺸﺖ ﺳﻪ ﺑﻌﺪي ﺑﻪﻫﻤﺮاه ﻣﻬﺎر ژن TGFbR2ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﻗﺎﺑﻞ ﺗﻮﺟﻪ 41±0/7ﺑﺮاﺑـﺮ ﺳـﻠﻮلﻫـﺎي CD34+ﺷـﺪ .وﻟـﻲ اﻓﺰاﻳﺶ ﻧﺴﺒﺖ ﺗﺰاﻳﺪ در دو ﺑﻌﺪي ﺳﺎده ﺑﻴﺶ از ﺳﻪ ﺑﻌﺪي ﺑﻮد و ﻧﻴﺰ ﺑﻴﺶﺗﺮﻳﻦ ﻣﻬﺎر ﺑﻴﺎن ژن ،ﺑﻴﺶﺗﺮﻳﻦ اﻓﺰاﻳﺶ در ﻣﺎرﻛﺮ ﺳﻄﺤﻲ ﺑﺎ آﻧﺎﻟﻴﺰ ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي در ﺣﺎﻟﺖ ﻛﺸﺖ دو ﺑﻌﺪي ﺳﺎده ﻧﺸﺎن داده ﺷﺪ ) .(P<0/05ﻧﺘﻴﺠﻪﮔﻴﺮي :ﺑﻨـﺎﺑﺮاﻳﻦ از ﻧﻈـﺮ *
ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،ﺗﻘﺎﻃﻊ ﺑﺰرگراه ﭼﻤﺮان و ﺟﻼل
آل اﺣﻤﺪ ،داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،ﮔﺮوه ﺑﻴﻮﺗﻜﻨﻮﻟﻮژي ﭘﺰﺷﻜﻲ .ﺻﻨﺪوق ﭘﺴﺘﻲ14115 -111 :
ﻣﻮﺛﺮ ﺑﻮدن ﺳﻴﺴﺘﻢ اﻧﺘﻘﺎل ،RNAiﻛﺸﺖ دو ﺑﻌﺪي ﺳﺎده ﻧﺴﺒﺖ ﺑﻪ ﺳﻪ ﺑﻌﺪي ﻛﺎرآﻣﺪﺗﺮ ﺑﻮد ﺑﻪﻃﻮري ﻛـﻪ ﺳـﻠﻮلﻫـﺎ آزادي ﻛﻢﺗﺮ داﺷﺘﻪ و ﺑﻴﺶﺗﺮ ﺑﺎ ﺳﻠﻮلﻫﺎي ﻻﻳﻪ ﻣﻐﺬي درﮔﻴﺮ ﺑﻮدﻧﺪ.
ﺗﻠﻔﻦ021-82883861 : E-mail: foroz@modares.ac.ir
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮن ﺑﻨﺪﻧﺎف ،ﺳﻠﻮلﻫﺎي ،USSCدارﺑﺴﺖ ،DBMﻣﺴﻴﺮ .siRNA ،TGF-b
ﺧﻮﻧﻲ ﻧﻴﺎز ﺑﻪ دوز ﺑﺎﻻﻳﻲ از ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز اﺳـﺖ .در اﺛـﺮ
ﻣﻘﺪﻣﻪ
ﺷﻴﻤﻲدرﻣﺎﻧﻲ ﻳﺎ اﺷﻌﻪ درﻣﺎﻧﻲ ،ﺳﻠﻮلﻫﺎ دﭼﺎر آﺳﻴﺐ ﻣﻲﺷﻮﻧﺪ و ﻧﻴﺎز ﺑـﻪ Hematopoietic Stem Cells
ﺗﺠﺪﻳﺪ آنﻫـﺎ ﻣـﻲﺑﺎﺷـﺪ .در اﻳـﻦ ﺷـﺮاﻳﻂ ﻛـﺸﺖ ﺳـﻠﻮﻟﻲ ﻳـﻚ روش
) (HSCsﺑﺎ دﺳﺖورزيﻫﺎي ژﻧﺘﻴﻜﻲ ﺑﻪ ﻣﻨﻈﻮر ﺗﻤـﺎﻳﺰ و ﻳـﺎ ﺗﺰاﻳـﺪ ﺑـﺮاي
ﻛﻤﻚﻛﻨﻨﺪه اﺳﺖ .در ﭘﻴﻮﻧﺪﻫﺎي ﭼﻨﺪﮔﺎﻧﻪ ﻛﻪ ﺑﻪ دﻟﻴـﻞ رد ﭘﻴﻮﻧـﺪ اﻧﺠـﺎم
اﻫﺪاف ﺑﺎﻟﻴﻨﻲ ﺑﻪﻛﺎر ﺑﺮده ﻣﻲﺷﻮﻧﺪ 1.ﺑـﺎ اﻓـﺰاﻳﺶ ﻣﺤﺘـﻮاي ﺳـﻠﻮلﻫـﺎي
ﻣﻲﺷﻮﻧﺪ ،ﻧﻴﺎز ﺑـﻪ ﺗﺰاﻳـﺪ ﺳـﻠﻮلﻫـﺎي ﺑﻨﻴـﺎدي اﺳـﺖ .ﻛـﺸﺖ و ﺗﺰاﻳـﺪ
ﺑﻨﻴﺎدي در ﺧﻮن ،درﻣﺎن ﻣـﻮﺛﺮﺗﺮ اﻧﺠـﺎم ﻣـﻲﺷـﻮد و ﺣﺘـﻲ ﻣـﻲﺗـﻮان از
ﺳﻠﻮلﻫﺎي CD34+ﺑﺎﻋﺚ ورود اﻳﻦ ﺳـﻠﻮلﻫـﺎ ﺑـﻪ ﻓـﺎز ﺗﻘـﺴﻴﻢ ﺳـﻠﻮﻟﻲ
ﺣﺠﻢﻫﺎي ﻛﻢ ﺧﻮن ﺑﻨﺪﻧﺎف ﻛﻪ در ﺣﺎﻟﺖ ﻋﺎدي ﻛﻨﺎر ﮔﺬاﺷﺘﻪ ﻣﻲﺷـﻮﻧﺪ
ﻣﻲﺷﻮد ﺑﻪﻃﻮري ﻛﻪ ﺑﺮاي ژن درﻣﺎﻧﻲ و اﻧﺘﻘـﺎل ژن وﻳﺮوﺳـﻲ ﻧﻴـﺎز ﺑـﻪ
Ex
Bone Marrow
اﻣﺮوزه ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧـﻮنﺳـﺎز
ﻧﻴﺰ اﺳﺘﻔﺎده ﻛﺮد .اﻣﻴﺪ اﺳﺖ ﻛﻪ ﺑﺎ ازدﻳﺎد اﻳـﻦ ﺳـﻠﻮلﻫـﺎ از ﻃﺮﻳــﻖ
vivoﺑـﻪ اﻳـﻦ ﻫـﺪف رﺳﻴـﺪ3.و 2ﺑـﺮاي درﻣـﺎن ﺑﺴﻴﺎري از ﺑﻴﻤـﺎريﻫﺎي
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺳﻠﻮﻟﻲ در ﻓﺎز ﺗﻘﺴﻴﻢ اﺳﺖ .در ﭘﻴﻮﻧـﺪ ﻣﻐـﺰ اﺳـﺘﺨﻮان )(BMT
Transplantﻛﻪ اﻓﺮاد ﺑﺴﻴﺎري ﺑﺎ آن ﺑﺮاي ﺑﻴﻤﺎريﻫﺎي ﻣﺎدرزادي
زﻫﺮااﻟﺴﺎدات ﻫﺎﺷﻤﻲ و ﻫﻤﻜﺎران
87
و اﻛﺘﺴﺎﺑﻲ ﺧﻮﻧﻲ درﻣﺎن ﻣﻲﺷﻮﻧﺪ 4،ﻧﻴﺎز ﺑـﻪ دوز ﺑـﺎﻻﻳﻲ از ﺳـﻠﻮلﻫـﺎي
ﻃﻲ ﭘﻴﻮﻧﺪﻫﺎي ﻣﺘﻮاﻟﻲ ﺷﺎﻫﺪ ﻧﻮﻋﻲ از دﺳﺖ رﻓﺘﻦ ذاﺗـﻲ ﺗﻮاﻧـﺎﻳﻲ ﺧـﻮد
ﺑﻨﻴﺎدي ﻳﺎ ﺳﻠﻮلﻫﺎي ﭘﻴﺶﺳﺎز ﺧﻮﻧﻲ ﻣﻲﺑﺎﺷﺪ 5.ﺳـﻠﻮلﻫـﺎي CD34+در
ﺗﻜﺜﻴﺮي در ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﻫﺴﺘﻴﻢ ﻛﻪ ﺑﻪ دﻟﻴﻞ ﺧـﺮوج اﻳـﻦ
BMTﺑﻴﺶﺗﺮ از ﻣﻨﺒﻊ ﺧﻮن ﺑﻨﺪﻧﺎف ﺑﻪ دﻟﻴﻞ ﭘﺎﻳﻴﻦ ﺑـﻮدن آﻟـﻮآﻧﺘﻲژنﻫـﺎ
ﺳﻠﻮلﻫﺎ از ﻓﺎز اوﻟﻴﻪ و ﺗﺎ ﺣﺪودي ﺑﻪ ﺳـﻤﺖ ﺗﻤـﺎﻳﺰ رﻓـﺘﻦ اﺳـﺖ 14.از
)Human Leukocyte Antigen (HLA
اﻳﻦرو ﺟﺴﺘﺠﻮي راﻫﻲ ﺑﺮاي ﺗﺰاﻳﺪ آنﻫﺎ در ﺟﻬﺖ ﻋﺪم ﺗﻤـﺎﻳﺰ ﻣﻮﻗـﺖ
ﺳﻄﺤﻲ و در ﻧﺘﻴﺠﻪ ﻋﺪم ﻧﻴﺎز ﺑﻪ ﺳﺎزﮔﺎري ﺑﺎﻻﻳﻲ ﺑﻴﻦ دﻫﻨﺪه و ﮔﻴﺮﻧـﺪه،
آنﻫﺎ و اﻟﺒﺘﻪ ﺑﺎ ﺣﻔﻆ ﭘﺘﺎﻧﺴﻴﻞ ﺗﻤﺎﻳﺰ ﺑﻪ ردهﻫﺎي ﻣﺨﺘﻠﻒ ﺧﻮﻧﻲ ،ﺿﺮوري
ﺗﻬﻴﻪ ﻣﻲﮔﺮدﻧﺪ 6.ﺗﻌﺪاد ﻛﻞ ﺳﻠﻮلﻫﺎي ﺑـﻪدﺳـﺖ آﻣـﺪه از اﻳـﻦ ﻣﻨﺒـﻊ در
ﻣﻲﺑﺎﺷﺪ .در اﻳﻦ راﺳﺘﺎ ﺑﺎ ﺑﻬﺮهﮔﻴﺮي از روشﻫﺎﻳﻲ ﻫﻤﺎﻧﻨﺪ اﻓﺰاﻳﺶ ﺑﻴـﺎن
ﺳﻄﺢ ﻛﻢﺗﺮي ﻣﻲﺑﺎﺷﺪ 7ﻛﻪ ﺑﺮاي ﻏﻠﺒﻪ ﺑﺮ اﻳﻦ ﻣﺸﻜﻞ ﭼﻨﺪ راه ﺣﻞ اراﻳـﻪ
ﻓﺎﻛﺘﻮرﻫﺎي روﻧﻮﻳﺴﻲ ﻛﻪ در اﻓﺰاﻳﺶ ﻓﻌﺎﻟﻴﺖ ﺧﻮد ﺗﻜﺜﻴﺮي ﻧﻘﺶ دارﻧـﺪ،
ﮔﺮدﻳﺪه اﺳﺖ :ﭘﻴﻮﻧﺪ ﻫﻢزﻣـﺎن ﭼﻨـﺪﻳﻦ واﺣـﺪ ،UCBﺗﺰرﻳـﻖ ﻫـﻢزﻣـﺎن
و ﻳﺎ ﻣﻬﺎر ﻓﺎﻛﺘﻮرﻫﺎي روﻧﻮﻳﺴﻲ ﻛﻪ ﺑﺎﻋﺚ ﻣﻬﺎر ﻓﻌﺎﻟﻴـﺖ ﺧـﻮد ﺗﻜﺜﻴـﺮي
BM
ﻣﻲﺷﻮﻧﺪ ،ﻣﻲﺗﻮان راﻫـﻲ ﻣﻨﺎﺳـﺐ ﺟﻬـﺖ رﺳـﻴﺪن ﺑـﻪ اﻓـﺰاﻳﺶ ﺗﺰاﻳـﺪ
UCB CD34+
ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﭘﻴﺪا ﻛﺮد .در اﻳﻦ ﺑﻴﻦ ﻋﻮاﻣﻞ ﺧﺎرج ﺳﻠﻮﻟﻲ ﻳﺎ اﮔﺰوژن
) (Alloantigenو آﻧﺘـﻲژنﻫـﺎي
ﺳﻠﻮلﻫﺎي UCB CD34+ﺑﺎ دوز ﻛﻢ ﻫﻤﺮاه ﺑﺎ ﺳﻠﻮلﻫـﺎي اﺳـﺘﺮوﻣﺎل ﺧﻮد ﺑﻴﻤﺎر ﻳﺎ ﻓﺮد اﻫﺪا ﻛﻨﻨﺪه ،ﺗﻜﺜﻴﺮ Ex vivoﺳـﻠﻮلﻫـﺎي
ﻣﺎﻧﻨﺪ ﻛـﺸﺖ ﺳـﻪ ﺑﻌـﺪي و ﺳـﭙﺲ ﺗﺰرﻳـﻖ ﺳـﻠﻮلﻫـﺎي ﺗﻜﺜﻴـﺮ ﺷـﺪه،
ﻧﻴﺰ در اﻟﻘﺎ ﻳﺎ ﻣﻬﺎر ﻓﻌﺎﻟﻴﺖ ﺧﻮد ﺗﻜﺜﻴﺮي ﺣﺎﻳﺰ اﻫﻤﻴﺖ ﻫﺴﺘﻨﺪ.
دﺳﺖﻛﺎري ژﻧﺘﻴﻜﻲ ﺳﻠﻮلﻫﺎي ﺑﻨﻴـﺎدي ﺟﻬـﺖ اﻓـﺰاﻳﺶ ﺗﻮاﻧـﺎﻳﻲ ﺧـﻮد
از ﺟﻤﻠﻪ ﻣﻬﻢﺗﺮﻳﻦ اﻳﻦ ﻋﻮاﻣﻞ ﻣﻲﺗﻮان ﺑﻪ ﻋﻮاﻣﻞ اﻟﻘﺎ ﻛﻨﻨﺪه ﺗﻜﺜﻴﺮ از
ﺗﺠﺪﻳﺪﺷﻮﻧﺪﮔﻲ و ﺗﺰاﻳﺪ اﻳﻦ ﺳﻠﻮلﻫﺎ9.و 8راه ﺣـﻞ اراﻳـﻪ ﺷـﺪه در اﻳـﻦ
ﻗﺒﻴــﻞ Notch ،Wnt ،BMP-4 ،Sonic hedgehogو دﻳﮕــﺮ ﻓﺎﻛﺘﻮرﻫــﺎي
ﺗﺤﻘﻴﻖ ،ادﻏﺎم دو راه ﺣﻞ آﺧﺮ اﺳﺖ .ﺑﺎﻳﺪ ﮔﻔﺖ ﭘﻮدرﻫﺎي اﺳﺘﺨﻮاﻧﻲ را
رﺷﺪ و ﻳﺎ ﻋﻮاﻣـﻞ ﻣﻬﺎرﻛﻨﻨـﺪه ﻣﺎﻧﻨـﺪ TGF-βو TNF-αو ﻧﻴـﺰ ﺑـﻪ ﺳـﺎﻳﺮ 15
Transforming Growth Factor-β
ﻣﻲﺗﻮان ﺑﻪﻋﻨﻮان دارﺑﺴﺖ ﺑﺮاي ﭘﻴﻮﻧﺪ اﺳـﺘﺨﻮان ﺑـﻪﻛـﺎر ﺑـﺮد زﻳـﺮا ﻛـﻪ
ﺳﺎﻳﺘﻮﻛﻴﻦﻫﺎي ﻣﻬﺎري اﺷﺎره ﻛـﺮد.
ﻛﺎراﻳﻲ ﺑﻴﺶﺗﺮ ﻧﺴﺒﺖ ﺑﻪ روشﻫﺎي ﮔﺬﺷﺘﻪ و ﺳﺎﻳﺮ ﻣﻮاد دارﻧﺪ .اﻳﻦ ﻣﻮاد
) (TGF-βﻳﻚ ﺳﺎﻳﺘﻮﻛﻴﻦ ﭼﻨﺪ ﻛـﺎره ) (Multifunctionalﻣـﻲﺑﺎﺷـﺪ .اﻳـﻦ
ﺧﻮد داراي ﻗﺪرت ﺗﺤﺮﻳﻚﻛﻨﻨﺪﮔﻲ ﺑﺮاي ﺑﺎﻓﺖ اﺳﺘﺨﻮان ﻫﺴﺘﻨﺪ زﻳﺮا ﻛﻪ
ﺳﺎﻳﺘﻮﻛﻴﻦ در ﻓﺮآﻳﻨﺪ ﺟﻨﻴﻦزاﻳﻲ ،ﺗﻤﺎﻳﺰ ﺳﻠﻮﻟﻲ ،ﻣﺮگ ﺑﺮﻧﺎﻣﻪرﻳـﺰي ﺷـﺪه
داراي ﭘــﺮوﺗﻴﻴﻦﻫــﺎي زﻣﻴﻨــﻪاي ﻛــﻼژن و ﻧﻴــﺰ ﻓﺎﻛﺘﻮرﻫــﺎي رﺷــﺪ ﻣﺜــﻞ
ﺳــﻠﻮﻟﻲ )آﭘﻮﭘﺘــﻮزﻳﺲ( و ﻧﻴــﺰ ﭼﺮﺧــﻪ ﺳــﻠﻮﻟﻲ دﺧﺎﻟــﺖ دارد و ﺗﻮﺳــﻂ
ﺧﺎﻧﻮادهي TGFﻣﻲﺑﺎﺷﻨﺪ ﻛﻪ ﺑﺎﻋﺚ وﺟﻮد ﺧﺎﺻﻴﺖ ﺗﺤﺮﻳﻚﻛﻨﻨـﺪﮔﻲ در
ﺳــﻠﻮلﻫــﺎي ﺧــﻮنﺳــﺎز ﺑــﻪ دو ﺻــﻮرت اﺗــﻮﻛﺮاﻳﻦ و ﭘــﺎراﻛﺮاﻳﻦ
اﻳـــﻦ دارﺑـــﺴﺖﻫـــﺎ ﺷـــﺪه اﺳـــﺖ11.و 10ﺗﺤﻘﻴﻘـــﺎت روي دارﺑـــﺴﺖ
18و17
ﺗﺮﺷﺢ ﻣﻲﺷﻮد
ﻛﻪ ﻣـﻲﺗﻮاﻧـﺪ ﺳـﻠﻮلﻫـﺎ را در ﻣﺮﺣﻠـﻪ G1ﭼﺮﺧـﻪ
Demineralized Boneﻧــﺸﺎن داده اﺳــﺖ ﻛــﻪ اﻳــﻦ
ﺳﻠﻮﻟﻲ ﻧﮕﻪ داﺷﺘﻪ و ﻣﻨﺠﺮ ﺑﻪ ﺗﻤﺎﻳﺰ ﺳﻠﻮلﻫﺎ ﺷﻮد 19-21.اﻳـﻦ ﺳـﺎﻳﺘﻮﻛﻴﻦ
دارﺑﺴﺖ ﺑﺮاي ﺗﺰاﻳﺪ ﺳﻠﻮلﻫـﺎي ﺧـﻮنﺳـﺎز ﻣﻨﺎﺳـﺐ ﻣـﻲﺑﺎﺷـﺪ 11.اﻳـﻦ
ﻣﻮﺟﺐ ﻣﻬﺎر ورود ﺑﻪ ﻣﻴﺘـﻮز و در ﻧﺘﻴﺠـﻪ ﺑﺎﻋـﺚ ﻣﻬـﺎر ﻓﻌﺎﻟﻴـﺖ ﺧـﻮد
)Matrix (DBM
دارﺑﺴﺖ ﻣﺎﺗﺮﻳﻜﺲ اﺳﺘﺨﻮاﻧﻲ اﺳﺖ ﻛﻪ از ﺑﺎﻓﺖ ﻃﺒﻴﻌﻲ اﺳﺘﺨﻮان ﺗﻬﻴﻪ و ﻣﻮاد ﻣﻌﺪﻧﻲ آن ﺑﺎ ﻛﻤﻚ اﺳﺘﺨﺮاج اﺳﻴﺪي ﺣﺬف ﺷـﺪه اﺳـﺖ ﺗـﺎ ﻣـﻮاد ﭘﺮوﺗﻴﻴﻨﻲ ﺑﺴﺘﺮ آﺷﻜﺎر ﺷﺪه و در اﺧﺘﻴﺎر ﺳﻠﻮلﻫﺎي ﻓﻴـﺪر ﻗـﺮار ﮔﻴﺮﻧـﺪ.
22-25
ﺗﻜﺜﻴﺮي اﺳﺖ.
ﺗﺤﻘﻴﻘﺎت ﺟﺪﻳﺪ ﻧﺸﺎندﻫﻨﺪه ﻧﻘﺶ اﻳﻦ ﺳﺎﻳﺘﻮﻛﻴﻦ در اﻟﻘـﺎي ﺣﺎﻟـﺖ 26
ﺧﻔﺘﮕﻲ در ﺑﺪن اﺳﺖ ﺣﺎل آنﻛﻪ در ﻣﻄﺎﻟﻌﺎت ﻗﺒﻠﻲ اﻳـﻦ ﻧﻘـﺶ ﺑـﺮاي 27
اﻳﻦ دارﺑﺴﺖ ﺑﻪ ﻫﻤـﺮاه ﻻﻳـﻪ ﺗﻐﺬﻳـﻪﻛﻨﻨـﺪهاي از ﺳـﻠﻮلﻫـﺎي ﭼـﺴﺒﻨﺪه
ﺳﺎﻳﺘﻮﻛﻴﻦ TGF-bرد ﺷﺪه ﺑﻮد .ﺑـﻪ دﻟﻴـﻞ اﻳـﻦﻛـﻪ در ﻣﺤـﻴﻂ ﻛـﺸﺖ
ﭘﺮوژﻧﻴﺘﻮر ﻣﺰاﻧﺸﻴﻤﻲ ﻳﺎ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺳﻮﻣﺎﺗﻴﻚ ﻏﻴﺮ ﻣﺤـﺪود ﺷـﺪه
آزﻣﺎﻳﺸﮕﺎﻫﻲ و در ﻛﺸﺖ ﻃﻮﻻﻧﻲﻣﺪت ﺳﻠﻮلﻫﺎي ﻣﻐﺰ اﺳـﺘﺨﻮان و ﻧﻴـﺰ
)13،Unrestricted Somatic Stem Cells (USSCو 12ﻣﻲﺗﻮاﻧﺪ ﺗﺎ ﺣـﺪودي
در ﺧﻮد ﺑﺎﻓﺖ دارﺑﺴﺖﻫﺎي ﻣﻬﻨﺪﺳﻲ ﺑﺎﻓﺖ ﺑﺎ ﻣﻨﺸﺎ ﻣﻐﺰ اﺳـﺘﺨﻮان ،ﻫـﻢ
رﻳﺰﻣﺤﻴﻂ ) (Microenvironmentﺳﻪ ﺑﻌﺪي ﻣﻐﺰ اﺳﺘﺨﻮان را ﺗﻘﻠﻴﺪ ﻛﻨﺪ.
ﭘﺮوﺗﻴﻴﻦ و ﻫﻢ RNAﭘﻴﺎﻣﺒﺮ آن ﻣﻮﺟﻮد اﺳﺖ ،ﺑﻨﺎﺑﺮاﻳﻦ ﺑـﺮاي ﻣﻬـﺎر اﻳـﻦ
ﻫﻤﻮاره دﺳﺖورزي ژﻧﺘﻴﻜﻲ روي ﻣﺴﻴﺮﻫﺎي ﻣﺨﺘﻠﻒ ﺑﻪ ﻣﻨﻈﻮر اﻓـﺰاﻳﺶ
ﻣﺴﻴﺮ ﺳﻴﮕﻨﺎلدﻫﻲ ﺑﻪ ﺳﺮاغ ﮔﻴﺮﻧﺪه ﻧﻮع دو ﻛﻪ ﮔﻴﺮﻧـﺪه اﺻـﻠﻲ در اﻳـﻦ
ﻗﺪرت ﺗﻜﺜﻴﺮ ﺳﻠﻮلﻫﺎ اﻧﺠـﺎم ﺷـﺪه اﺳـﺖ .اﻟﻘـﺎي ﻓﺎﻛﺘﻮرﻫـﺎي رﺷـﺪ و
ﻣﺴﻴﺮ اﺳﺖ ﻣﻲروﻳﻢ .اﻳـﻦ ﮔﻴﺮﻧـﺪه ﺳـﺮﻳﻦ-ﺗﺮﻳـﻮﻧﻴﻦ ﻛﻴﻨـﺎزي ﻋﺮﺿـﻲ
روﻧﻮﻳﺴﻲ و ﻳﺎ ﻣﻬﺎر ﭘﺎرهاي دﻳﮕﺮ از ﻓﺎﻛﺘﻮرﻫـﺎ و ﺳـﺎﻳﺘﻮﻛﻴﻦﻫـﺎ در اﻳـﻦ
ﻏﺸﺎﻳﻲ ) (Transmembraneو ﺑﺎ ﺣﺬف آن TGF-β ،ﺷﻨﺎﺳـﺎﻳﻲ ﻧـﺸﺪه و
زﻣﻴﻨﻪ ﺑﺮرﺳﻲ ﺷﺪهاﻧﺪ .در ﻃﻲ ﻓﺮاﻳﻨﺪ ﺗﺰاﻳﺪ ،ﺳﻠﻮلﻫﺎي ﺑﻨﻴـﺎدي ﺗﻮاﻧـﺎﻳﻲ
ﻣﺴﻴﺮ ﺳﻴﮕﻨﺎلدﻫﻲ ﻣﺘﻮﻗﻒ ﻣﻲﺷﻮد .ﺑﻨﺎﺑﺮاﻳﻦ در اﻳﻦ ﺗﺤﻘﻴﻖ ﺳـﻌﻲ ﺷـﺪه
ﺑﻨﻴﺎدي ﺧﻮد را از دﺳﺖ داده و ﺑﻪ ﺳﻤﺖ ﺗﻤﺎﻳﺰ ﻣﻲروﻧﺪ .ﻫـﻢﭼﻨـﻴﻦ در
اﺳﺖ ﺗﺎ ﺑﺎ اﻧﺠﺎم ﻫﻢزﻣﺎن اﺳﺘﻔﺎده از ﻛـﺸﺖ ﺳـﻪ ﺑﻌـﺪي و ﻣﻬـﺎر ﻣـﺴﻴﺮ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
88
ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﺎ ﺗﻜﻨﻴﻚ RNAiدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز
TGF-βﺑﻪ ﺗﺰاﻳﺪ ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ از ﺳﻠﻮلﻫﺎي ﺑﻨﻴـﺎدي ﺧـﻮنﺳـﺎز رﺳـﻴﺪ.
ﻣﻴﻠﻲﻣﺘﺮ ﺑﺮش داده ﺷﺪﻧﺪ .اﻳﻦ ﻣﻜﻌـﺐﻫـﺎ در ﭘﻠﻴـﺖ ﺷـﺶ ﺧﺎﻧـﻪ و ﺑـﻪ
ﻫﻢﭼﻨﻴﻦ ﺳﺎﺧﺘﺎر ﺷﺒﻴﻪﺳﺎزي ﺷﺪه آﺷﻴﺎﻧﻪ ﺳـﻠﻮﻟﻲ ) (Nicheﺳـﻠﻮلﻫـﺎي
ﺻﻮرت ﻳﻚ ردﻳﻒ و ﺗﺎ ﺣﺪ اﻣﻜﺎن ﻓﺸﺮده ،ﭼﻴﺪه ﺷﺪﻧﺪ .ﺳﭙﺲ ﺑﻪ روي
ﺑﻨﻴﺎدي ﻣﻲﺗﻮاﻧﺪ ﺑﻪ ﻋﻨﻮان ﻣﺪﻟﻲ ﺑﺮاي ﺣﺎﻟﺖ In vivoﺑﺎﺷﺪ ﺑﻪﻃﻮري ﻛـﻪ
اﻳﻦ ﻗﻄﻌﺎت ﺳﻮﺳﭙﺎﻧﺴﻴﻮن ﻏﻠﻴﻆ ﺳـﻠﻮﻟﻲ در ﻣﺤـﻴﻂ DMEMﺑـﻪ ﻫﻤـﺮاه
ﺳﺮﻛﻮب ﻳﻚ ﻣﺴﻴﺮ ﺳﻴﮕﻨﺎلدﻫـﻲ ﺑـﺎ ﻛﻤـﻚ ﺗﻜﻨﻴـﻚ RNAiدر ﻣﺤـﻴﻂ
) FBSﺑﻪ ﻣﻴﺰان %30در ﺣﺠﻢ ﻣﺤﻴﻂ ﻛﺸﺖ( اﺿﺎﻓﻪ ﮔﺸﺖ و ﺑـﻪ ﻣـﺪت
siRNA
12ﺳﺎﻋﺖ اﻧﻜﻮﺑﻪ ﺷﺪ .ﺳﭙﺲ ﻫﺮ ﻗﻄﻌـﻪ دارﺑـﺴﺖ ﺑـﻪ آراﻣـﻲ ﺑـﻪ ﻳـﻚ
آزﻣﺎﻳﺸﮕﺎه ﻣﻮرد ارزﻳﺎﺑﻲ ﻗﺮار ﮔﻴﺮد ﺗﺎ ﺷﺪت اﺛﺮ ﺳﻴـﺴﺘﻢ اﻧﺘﻘـﺎل در ﺣﺎﻟﺖ دو ﺑﻌﺪي و ﺳﻪ ﺑﻌﺪي ﺑﺮرﺳﻲ ﺷﻮد.
ﭼﺎﻫﻚ ﭘﻠﻴﺖ 48ﺗﺎﻳﻲ ﻣﻨﺘﻘﻞ ﺷﺪه و ﺑﻪ ﻣﺪت ﺳﻪ روز اﻧﻜﻮﺑﻪ ﺷـﺪﻧﺪ ﺗـﺎ ﺗﺮاﻛﻢ %80ﺑﻪدﺳﺖ آﻳﺪ .در اﻳﻦ ﻣﺪت ﺳﻠﻮلﻫﺎي ﭼﺴﺒﻨﺪه دوﻛﻲ ﺷـﻜﻞ USSCاﺗﺼﺎﻻت ﺧﻮد را ﺑﺎ ﻳﻚدﻳﮕﺮ و ﺑﺎ دارﺑﺴﺖ ﻣﺤﻜﻢ ﻛـﺮده و روي
روش ﺑﺮرﺳﻲ
ﻣﺤﻠﻲ ﻛﻪ ﺟﺎيﮔﻴﺮي ﻛﺮدهاﻧﺪ ﭘﻬﻦ و ﺑﺎز ﻣﻲﺷﻮﻧﺪ .ﺑﻌـﺪ از رﺳـﻴﺪن ﺑـﻪ ﻧﻮع ﻣﻄﺎﻟﻌﻪ ﻋﻠﻤـﻲ ﭘﮋوﻫـﺸﻲ ﻣـﻲﺑﺎﺷـﺪ ﻛـﻪ در ﺳـﺎل 1389و در
اﻳﻦ ﻣﺮﺣﻠﻪ ﭼﻨﺪ دارﺑﺴﺖ ﺑـﺮاي اﻧﺠـﺎم ﻋﻜـﺲﺑـﺮداري ﻣﻴﻜﺮوﺳـﻜﻮپ اﻟﻜﺘﺮوﻧــﻲ روﺑــﺸﻲ ) (Scanning electron microscopeﺑﺮداﺷــﺘﻪ )در
داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس اﻧﺠﺎم ﺷﺪ. ﺟﻤﻊآوري ﻧﻤﻮﻧﻪ و ﺟﺪاﺳﺎزي ﺳﻠﻮلﻫﺎي :USSCواﺣﺪﻫﺎي ﺧـﻮن
داﻧﺸﻜﺪه اﻟﻜﺘﺮوﻧﻴﻚ داﻧﺸﮕﺎه ﺗﻬﺮان آزﻣﺎﻳﺸﮕﺎه ﻻﻳـﻪ ﻧـﺎزك( و ﺑﻘﻴـﻪ ﺑـﺎ
ﺑﻨـﺪﻧﺎف ﺑـﺮ اﺳـﺎس راﻫﻜﺎرﻫـﺎي ﻣـﺼﻮب ﻛﻤﻴﺘـﻪ اﺧـﻼق ﭘﺰﺷــﻜﻲ در
ﻣﻴﺘﻮﻣﺎﻳﺴﻴﻦ Cﻏﻴﺮﻓﻌﺎل ﺷﺪﻧﺪ .ﻏﻴﺮﻓﻌﺎلﺳﺎزي ﺑﺎ ﻛﻤﻚ اﺷـﻌﻪ ﮔﺎﻣـﺎ ﻧﻴـﺰ
داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس و ﺑﻴﻤﺎرﺳﺘﺎن ﺷﺮﻳﻌﺘﻲ ﺟﻤﻊآوري ﺷﺪﻧﺪ .از اﻳـﻦ
اﻧﺠﺎم ﻣـﻲﺷـﻮد وﻟـﻲ در اﻳﻨﺠـﺎ اﺳـﻼﻳﺲﻫـﺎي دارﺑـﺴﺖ DBMداراي
اﻓﺮاد ﺑﺮاي ﮔﺮﻓﺘﻦ ﻧﻤﻮﻧﻪ ﺑﻪﻣﻨﻈﻮر ﺗﻬﻴﻪ ﺟﺎﻣﻌﻪ آﻣﺎري رﺿﺎﻳﺖﻧﺎﻣﻪ ﮔﺮﻓﺘـﻪ
ﺗﺨﻠﺨﻞ ﻫﺴﺘﻨﺪ و ﻧﻤﻲﺗﻮان ﺑﻪﻃﻮر ﻛﺎﻣﻞ ﺗﻤـﺎم ﻧﻘـﺎط را ﺗﺤـﺖ ﭘﻮﺷـﺶ
ﺷﺪ .در اﺑﺘﺪا ﺑﺎ روش ﻣﻌﻤﻮل ﻓﺎﻳﻜﻮل ،ﺳﻠﻮلﻫﺎي ﺗـﻚﻫـﺴﺘﻪاي ﺧـﻮن
اﺷﻌﻪ ﻗﺮار داد.
ﺑﻨﺪﻧﺎف ﺟﺪا ﺷﺪه و ﺳﭙﺲ ﺳﻠﻮلﻫﺎي USSCﺑﺮ اﺳﺎس ﭘﺮوﺗﻜﻞ
Kogler
28-30
ﻫﻢﻛﺸﺘﻲ ﺳـﻠﻮلﻫـﺎي
CD34+
ﺑـﺎ :USSCدر ﻧﻬﺎﻳـﺖ ﺳـﻠﻮلﻫـﺎي
CD34+ﺑﺎ روش ﻣﻌﻤـﻮل ﻓـﺎﻳﻜﻮل و ﺳـﭙﺲ ﺑـﺎ اﺳـﺘﻔﺎده از آﻧﺘـﻲﺑـﺎدي
G.از ﺧﻮن ﺑﻨﺪﻧﺎف ﺟﺪاﺳﺎزي ،ﻧﮕﻪداري و ﭘﺎﺳﺎژ داده ﺷﺪﻧﺪ.
ﻛـــﺸﺖ ﺳـــﻠﻮلﻫـــﺎي USSCروي ﭼﺎﻫـــﻚ و دارﺑـــﺴﺖ :DBM
ﻧـﺸﺎندار ﺷـﺪه ﺑـﺎ ﻣﮕﻨـﺖ
(Miltenyi Biotech, BergischGladbach,
ﺳﻠﻮلﻫﺎي USSCﺟﺪاﺳﺎزي ﺷﺪه ،روي ﭼﺎﻫﻚﻫﺎي 48ﺗﺎﻳﻲ ﺑﻪ ﻋﻨـﻮان
) Germanyو ﺳــﺘﻮنﻫــﺎي روش
ﻻﻳﻪ ﻣﻐﺬي و ﭘﻮﺷـﺎﻧﻨﺪه ﺳـﻄﺢ دو ﺑﻌـﺪي ﻛـﺸﺖ داده ﺷـﺪﻧﺪ .ﭘـﺲ از
) Miltenyi Biotechﻣﺘﻌﻠﻖ ﺑـﻪ ﻛـﺸﻮر آﻟﻤـﺎن( ﻃﺒـﻖ ﭘﺮوﺗﻜـﻞ ﺷـﺮﻛﺖ
C
ﺳﺎزﻧﺪه ،از ﺧﻮن ﺑﻨﺪﻧﺎف ﺟﺪاﺳﺎزي ﺷﺪﻧﺪ .ﭘﺲ از ﺗﻌﻴـﻴﻦ ﻣﻴـﺰان زﻧـﺪه
) (Mitomycinﺑﻪ ﻣﻴـﺰان 10µg/mlﺟﻬـﺖ ﻫـﻢﻛـﺸﺘﻲ ﺑـﺎ ﺳـﻠﻮلﻫـﺎي
ﺑﻮدن ﺳﻠﻮلﻫﺎ و ﺗﺎﻳﻴﺪ ﺑﺎ روش ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي ،ﺑﻪ ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ داده
ﺧﻮنﺳﺎز CD34+ﻏﻴﺮﻓﻌﺎل ﺷﺪﻧﺪ .ﺑﻪﻃﻮري ﻛـﻪ ﻓﻌﺎﻟﻴـﺖ ﻣﻴﺘـﻮزي ﻻﻳـﻪ
ﺷﺪﻧﺪ:
رﺳﻴﺪن ﺑﻪ ﺗﺮاﻛﻢ ،%80اﻳﻦ ﻻﻳـﻪ ﺳـﻠﻮلﻫـﺎي USSCﺑـﺎ ﻣﻴﺘﻮﻣﺎﻳـﺴﻴﻦ
ﭘﺸﺘﻴﺒﺎن ﻣﺘﻮﻗﻒ ﺷﺪ .ﻣﻴﺘﻮﻣﺎﻳﺴﻴﻦ ﻓﻌﺎﻟﻴﺖ آﻧﺘﻲﺑﻴﻮﺗﻴﻚ و ﺿـﺪ ﺗﻮﻣـﻮري 31
دارد و ﺑﺎ اﺗﺼﺎل ﻣﺘﻘﺎﻃﻊ ﺑﻪ DNAاز ﺗﻜﺜﻴﺮ ﺳﻠﻮﻟﻲ ﺟﻠﻮﮔﻴﺮي ﻣﻲﻛﻨـﺪ.
LS separation columns- MACS
ﺣﺎﻟﺖ اول :ﻛـﺸﺖ ﺳـﺎده ﺳـﻠﻮلﻫـﺎي CD34+در ﭼﺎﻫـﻚ ﭘﻠﻴـﺖ 48ﺗﺎﻳﻲ ﺑﺪون ﻓﻴﺪر و ﺑﺪون دارﺑﺴﺖ.
ﺑﺮاي ﭘﻮﺷﺶ دادن ﺳـﻠﻮلﻫـﺎي اﺳـﺘﺮوﻣﺎل USSCروي اﺳـﻼﻳﺲﻫـﺎي
ﺣﺎﻟﺖ دوم :ﻫﻢ ﻛﺸﺘﻲ ﺳﻠﻮلﻫﺎي ﺧﻮنﺳﺎز ﺑﺎ ﻓﻴﺪري از ﺳﻠﻮلﻫﺎي
دارﺑﺴﺖ ) DBMﺗﻬﻴﻪ ﺷﺪه از ﻣﺮﻛﺰ ﺑﺎﻧﻚ ﭘﻴﻮﻧﺪ ﻣﻐﺰ اﺳﺘﺨﻮان اﻳﺮان( ﺑـﻪ
.USSCﺣﺎﻟﺖ ﺳﻮم :ﻫﻢﻛﺸﺘﻲ ﺳﻠﻮلﻫﺎي ﺧﻮنﺳﺎز ﺑﺎ ﻓﻴﺪر و ﺑﻪ ﻫﻤـﺮاه
T75
دارﺑﺴﺖ .DBMدر ﻛﻠﻴﻪ اﻳﻦ ﺳﻪ ﺣﺎﻟـﺖ از ﻣﺤـﻴﻂ ﻛـﺸﺖ اﺧﺘـﺼﺎﺻﻲ
ﺑﺎ ﺗﺮاﻛﻢ %80اﺳﺖ )در ﻣﺠﻤﻮع 3×106ﺳﻠﻮل( .ﻗﺒـﻞ از ﻋﻤـﻞ ﻛﺎﺷـﺖ
ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﻳﻌﻨﻲ ﻣﺤﻴﻂ ) Stemspanﻓﺮم ﺗﺠـﺎري آن از
ﺳﻠﻮﻟﻲ ،دارﺑﺴﺖﻫﺎ ﺑﺎﻳﺪ ﺑﺮاي اﺗﺼﺎل ﺳﻠﻮلﻫﺎ ﻣﺴﺘﻌﺪ ﺷـﺪه و ﻣﻨﺎﻓـﺬ آن
StemSpan
ﻋﻨﻮان ﻻﻳﻪ ﻣﻐﺬي و ﭘﻮﺷﺎﻧﻨﺪه ﺳﻄﺢ ﺳﻪ ﺑﻌﺪي ﻧﻴﺎز ﺑﻪ ﺳﻪ ﻓﻼﺳـﻚ
ﺷﺮﻛﺖ Stem cell technologiesدر ﻛﺸﻮر ﻛﺎﻧـﺎدا ﺑـﻪ ﻧـﺎم
ﺑﻨﻴﺎدي Stem Cell Factor
ﺑﺎز ﺷﻮﻧﺪ .ﺑﺪﻳﻦ ﻣﻨﻈﻮر ﺑﻪ ﻣﺪت 24ﺳﺎﻋﺖ اﺳﻼﻳﺲﻫـﺎي دارﺑـﺴﺖ در
SFEMﺗﻬﻴﻪ ﺷﺪ( ﺑﻪ ﻫﻤﺮاه ﻓﺎﻛﺘﻮر رﺷﺪ ﺳﻠﻮل
ژﻻﺗﻴﻦ %0/1در ﺑﺎﻓﺮ PBSﻏﻮﻃﻪور ﮔﺸﺘﻪ و اﻧﻜﻮﺑﻪ ﺷﺪﻧﺪ .ﭘـﺲ از اﻳـﻦ
) ،(SCFﺗﺮوﻣﺒﻮﭘـﻮﻳﺘﻴﻦ ) flt-3 ،(Thrombopoietin –TPOﻟﻴﮕﺎﻧـﺪ
ﻣﺪت اﺳﻼﻳﺲﻫﺎي دارﺑﺴﺖ ﺑﻪ ﻣﻜﻌﺐﻫﺎﻳﻲ ﺑـﺎ ﻗﻄـﺮ ﺷـﺶ ﺗـﺎ ﻫـﺸﺖ
) ،like tyrosine kinase 3-ligandﻫﺮ ﻳﻚ ﺑﻪ ﻣﻴـﺰان 50ng/mlاﺳـﺘﻔﺎده
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
(FMS-
زﻫﺮااﻟﺴﺎدات ﻫﺎﺷﻤﻲ و ﻫﻤﻜﺎران
89
ﮔﺸﺖ TGFbR 2 .ﻋﻠﻴﻪ 2-4SiRNAﺗﺮاﻧﺴﻔﻜﺸﻦ :ﺑﺮاي اﻧﺠﺎم ﺗﺮاﻧﺴﻔﻜﺸﻦ
ﺑﺮاي ﻃﺮاﺣﻲ آﻏﺎزﮔﺮ دو ژن ﺑﻪﻛﺎر رﻓﺘﻪ در اﻳـﻦ ﺗﺤﻘﻴـﻖ )ﺑﺘـﺎ-اﻛﺘـﻴﻦ و
ﻛﻠﻴﻪ ﻣـﻮاد از ﺷـﺮﻛﺖ Invitrogenﺗﻬﻴـﻪ ﮔـﺸﺖ .در اﻳـﻦﺟـﺎ از روش
(TGFbR2از ﻧﺮماﻓﺰار Oligo 6اﺳﺘﻔﺎده ﺷﺪ .ﺑﻪ ﺗﺮﺗﻴـﺐ ﭘـﻨﺞ دﻗﻴﻘـﻪ در º
º
º
º
ﺗﺮاﻧﺴﻔﻜﺸﻦ ﺟﻠﻮﻳﻲ ) (Forward transfectionاﺳﺘﻔﺎده ﺷﺪ ﺑﻪﻃﻮري ﻛـﻪ
C
روز ﻗﺒــﻞ از ﺗﺮاﻧﺴﻔﻜــﺸﻦ ﺣــﺪود 25ﺗــﺎ 35ﻫــﺰار ﺳــﻠﻮل در 200
دﻗﻴﻘﻪ در 72 ºCﺑﺮاي ﻣﺮاﺣﻞ واﺳﺮﺷﺘﮕﻲ اوﻟﻴﻪ )،(Initial denaturation
ﻣﻴﻜﺮوﻟﻴﺘﺮ ﻣﺤﻴﻂ ﻓﺎﻗﺪ آﻧﺘﻲﺑﻴﻮﺗﻴﻚ و ﺳﺮم ﺑﻪ ﻫﺮ ﺧﺎﻧﻪ ﭘﻠﻴـﺖ 48ﺧﺎﻧـﻪ
واﺳﺮﺷﺘﮕﻲ ﺛﺎﻧﻮﻳﻪ ،اﺗـﺼﺎل ) ،(Annealingﺑـﺴﻂ ) (Extensionو ﺑـﺴﻂ
در ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ :ﻛﺸﺖ ﺳﺎده ،ﻛﺸﺖ روي ﻓﻴﺪر و ﻛﺸﺖ ﺳﻪ ﺑﻌﺪي
ﻧﻬﺎﻳﻲ ﺑﻪﻛﺎر ﺑﺮده ﺷﺪ.
15 ،95ﺛﺎﻧﻴﻪ در
C
15 ،95ﺛﺎﻧﻴﻪ در
C
25 ،56ﺛﺎﻧﻴـﻪ در
C
10 ،72
در DBMﻣﻨﺘﻘﻞ ﺷﺪ .ﺑﺮاي ﻫﺮ ﺣﺎﻟﺖ ﻛﺸﺖ ،دو ﮔـﺮوه در ﻧﻈـﺮ ﮔﺮﻓﺘـﻪ
اﻳﻦ ﻣﺮاﺣـﻞ ﺑـﺮاي 45ﭼﺮﺧـﻪ ﺗﻜـﺮار ﮔـﺸﺖ و در ﻧﻬﺎﻳـﺖ ذوب
ﺷﺪ :ﮔﺮوه اول ﺑﺎ Stealth Select RNAi TM siRNAﺑﺮ ﻋﻠﻴﻪ TGFbR2و
) (Meltingدر Rotor-Gene Real-Time PCRاﻧﺠﺎم ﺷﺪ .واﻛﻨﺶﻫـﺎ ﺑـﻪ
StealthTMﺗﻴﻤـﺎر
ﺻﻮرت دوﺗﺎﻳﻲ ﺑﻮد و ﻣﻴﺎﻧﮕﻴﻦ آنﻫﺎ اراﻳﻪ ﺷﺪ .ﺑﺮاي اﻧﺪازهﮔﻴﺮي ﻣﻘـﺪار
ﺷﺪﻧﺪ .ﺑﺮاي ﺑﺮرﺳﻲ ﻣﻴﺰان ﺗﺮاﻧﺴﻔﻜﺸﻦ در ﮔـﺮوه ﻛـﺸﺖ ﺳـﺎده ﻧﻴـﺰ از
و ﺑﻴﺎن ﻧﺴﺒﻲ ژن ) (Relative quantitationاز روش Pfafflاﺳﺘﻔﺎده ﺷـﺪ
Block-iT TM alexa fluor red fluorescent oligoاﺳﺘﻔﺎده ﺷـﺪ .ﻛﻠﻴـﻪ
ﻛﻪ در آن ﻣﻘﺪار ) Threshold Cycle (TCﺑﺮاي ژن ﻫﺪف ﻫﻢ در ﺣﺎﻟـﺖ
اﻟﻴﮕﻮﻧﻮﻛﻠﻴﻮﺗﻴﺪﻫﺎي ﻣﺬﻛﻮر ﺑـﻪ ﻣﻴـﺰان 2/4ﭘﻴﻜﻮﻣـﻮل در 20ﻣﻴﻜﺮوﻟﻴﺘـﺮ
ﻛﻨﺘﺮل و ﻫﻢ در ﺣﺎﻟﺖ ﺗﻴﻤﺎر ﺷﺪه ﺑﺎ siRNAوﻧﻴـﺰ ژن ﻛﻨﺘـﺮل درون زاد
Opti-MEMدر ﻳـــــﻚ ﺗﻴـــــﻮب و ﺣـــــﺪود 0/4ﻣﻴﻜﺮوﻟﻴﺘـــــﺮ از
)در اﻳﻦﺟﺎ از ژن ﺑﺘﺎ-اﻛﺘﻴﻦ ﻣﻮرد ارزﻳﺎﺑﻲ ﻗﺮار ﮔﺮﻓـﺖ( ﻫـﻢ در ﺣﺎﻟـﺖ
Lipofectamine™ RNAiMAXدر 20ﻣﻴﻜﺮوﻟﻴﺘﺮ Opti-MEMدر ﺗﻴﻮب
ﻛﻨﺘﺮل و ﻫﻢ در ﺣﺎﻟﺖ ﺗﻴﻤﺎر ﺷـﺪه ﺑـﺎ ،siRNAدر ﻓﺮﻣـﻮل Pfafflﻗـﺮار
دﻳﮕﺮي اﺿﺎﻓﻪ ﺷﺪﻧﺪ .ﭘﺲ از ﮔﺬﺷﺖ زﻣﺎن ﭘـﻨﺞ دﻗﻴﻘـﻪ اﻧﻜﻮﺑﺎﺳـﻴﻮن در
داده ﺷﺪ ﺗﺎ ﺑﻴﺎن ژن ﺑﺎ ژن ﻛﻨﺘﺮل درون زاد ﻧﺮﻣـﺎﻟﻴﺰه ﺷـﻮد و در ﻧﻬﺎﻳـﺖ
دﻣﺎي اﺗﺎق ،ﻣﺤﺘﻮﻳﺎت دو ﺗﻴﻮب ﺑﻪ ﻳﻚدﻳﮕـﺮ اﺿـﺎﻓﻪ ﺷـﺪﻧﺪ و ﭘـﺲ از
ﻛﺎﻫﺶ ﺑﻴﺎن ژن ﺑﻪدﺳﺖ آﻣﺪ.
ﮔـﺮوه دوم ﺑـﺎ
RNAi negative control duplexes
ﮔﺬﺷﺖ 20دﻗﻴﻘﻪ ﻛﻤﭙﻠﻜﺲ ﻧﻬﺎﻳﻲ ﺗﺸﻜﻴﻞ ﺷﺪه و آن را ﺑـﻪ ﺧﺎﻧـﻪﻫـﺎي
ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي :ﻗﺒﻞ و ﺑﻌـﺪ از ﺗﻴﻤـﺎر ﺑـﺎ RNAiو ازدﻳـﺎد ﺳـﻠﻮﻟﻲ،
ﭘﻠﻴﺖ اﺿﺎﻓﻪ ﻣﻲﻛﻨﻴﻢ .ﺑﺎ اﺿﺎﻓﻪ ﻛﺮدن اﻳﻦ ﻛﻤﭙﻠﻜﺲ ﺣﺠﻢ ﻧﻬﺎﻳﻲ ﺑﻪ 240
ﺳــﻠﻮلﻫــﺎي CD34+از ﻧﻈــﺮ ﻣــﺎرﻛﺮ ﺳــﻄﺢ ﺳــﻠﻮﻟﻲ ﺑــﺎ اﺳــﺘﻔﺎده از
ﻣﻴﻜﺮوﻟﻴﺘﺮ ﻣﻲرﺳﺪ ﻛﻪ ﻏﻠﻈـﺖ ﻧﻬـﺎﻳﻲ اﻟﻴﮕﻮﻧﻮﻛﻠﻴﻮﺗﻴـﺪ ﺑـﻪ 10ﻧـﺎﻧﻮﻣﻮل
ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي PARTEC Germanyارزﻳﺎﺑﻲ ﺷﺪﻧﺪ .ﺗﻌـﺪاد 105ﺳـﻠﻮل
ﻣﻲرﺳﺪ .ﺑﻪ آراﻣﻲ ﭘﻠﻴﺖ را ﺑﻪ ﺳـﻤﺖ ﺟﻠـﻮ و ﻋﻘـﺐ ﺗﻜـﺎن داده ﺗـﺎ ﺑـﻪ
ﺷﻤﺎرش ﺷﺪه و ﺑﺎ ﺑﺎﻓﺮ PBSﺣﺎوي FBS %5ﺷﺴﺘﺸﻮ ﺷﺪه و ﺑﺎ اﺳـﺘﻔﺎده
ﺧﻮﺑﻲ ﻛﻤﭙﻠﻜﺲ ﺑﺎ ﻣﺤﻴﻂ ﻛـﺸﺖ ﻣﺨﻠـﻮط ﺷـﻮد .ﺳـﭙﺲ ﭘﻠﻴـﺖﻫـﺎ در
از آﻧﺘـﻲﺑـﺎديﻫـﺎي ﻛﻮﻧﮋوﮔـﻪ ﺷـﺪه ﺑـﺎ ﻓﻠـﻮروﻛﺮوم
(Fluorescein
اﻧﻜﻮﺑﺎﺗﻮر 37 ºCو %5 CO2ﮔﺬاﺷﺘﻪ و ﻣﻲﺗـﻮان ﺑﻌـﺪ از ﺷـﺶ ﺳـﺎﻋﺖ
) Isothiocyanate (FITC)- conjugated Antibodiesرﻧـﮓآﻣﻴـﺰي ﺿـﺪ
ﻣﺤﻴﻂ ﺳﻠﻮﻟﻲ را ﺗﻌﻮﻳﺾ ﻛﺮد.
CD34اﻧﺠﺎم ﺷﺪ .از آﻧﺘﻲﺑﺎدي FITC-mouse IgG1ﺑﻪ ﻋﻨـﻮان اﻳﺰوﺗﻴـﭗ
اﻧﺪازهﮔﻴﺮي ﻛﻤﻲ ﻣﻴﺰان ﺳﺮﻛﻮب ﺑﻴـﺎن ژن TGFbR2ﺑـﺎ اﺳـﺘﻔﺎده از
ﻛﻨﺘﺮل ﺑﺮاي ﺗﻀﻤﻴﻦ اﺧﺘﺼﺎﺻﻲ ﺑﻮدن واﻛﻨﺶ اﺳﺘﻔﺎده ﺷﺪ .ﺳﻠﻮلﻫـﺎ در
Real-Time PCRﻛﻤﻲ ) :Quantitative Real-Time PCR (QRT-PCRﺑﺮ
ﻧﺎﺣﻴﻪاي ﻛﻪ داراي ﭘﺮاﻛﻨﺶ ﻧﻮري ﭘـﺎﻳﻴﻦ ﺑﻮدﻧـﺪ ﺑـﻪ ﻋﻨـﻮان
Low side
اﺳﺎس ﭘﺮوﺗﻜﻞ ﺷـﺮﻛﺖ ﺳـﻴﻨﺎژن و ﻣﺤﻠـﻮل RNA ،RNXTM-plusﻛـﻞ
scatter-gateﺗﻌﻴــﻴﻦ ﺷــﺪﻧﺪ و ﺑــﺮاي ارزﻳــﺎﺑﻲ از ﻧــﺮماﻓــﺰار
ﺳﻠﻮﻟﻲ ﺗﺨﻠﻴﺺ ﮔﺸﺖ .اﻳﻦ ﻋﻤﻞ در ﻓﻮاﺻﻞ 48و 72ﺳـﺎﻋﺖ ﭘـﺲ از
اﺳﺘﻔﺎده ﺷﺪ.
)(Fermentase
آزﻣﻮن ﻛﻠﻮﻧﻲزاﻳﻲ :ﺳﻠﻮلﻫﺎي ازدﻳﺎد ﺷﺪه از ﮔﺮوه ﻛﻨﺘﺮل و آزﻣـﻮن
Revert AidTM M-
ﺑﺮاي ﺑﺮرﺳﻲ ﻛﻠﻨﻲزاﻳﻲ ﺑﺎ اﺳﺘﻔﺎده از ﻣﺤـﻴﻂ ) Methocultﻓـﺮم ﺗﺠـﺎري
MuLVو ﭘﺮاﻳﻤــﺮ Random hexamerﺑــﺮ
Stem
ﺗﺮاﻧﺴﻔﻜﺸﻦ اﻧﺠﺎم ﺷﺪ .ﺳﭙﺲ ﻣﺤﻠﻮل ﺣﺎﺻﻞ ﺷـﺪه ﺑـﺎ DNaseIﺗﻴﻤﺎر ﮔﺸﺘﻪ و ﺑﺮاي ﺳﻨﺘﺰ cDNAاز آﻧـﺰﻳﻢ Reverse Transcriptase
FloMax
اﺳﺎس ﺷﺮﻛﺖ ﺳﺎزﻧﺪه ) (Fermentaseاﺳﺘﻔﺎده ﺷﺪ .ﺑﺮاي اﻧﺠﺎم واﻛـﻨﺶ
آن (Methocult H4435 Enrichedو ﭘﺮوﺗﻜﻞ ﺷـﺮﻛﺖ ﺳـﺎزﻧﺪه ) cell technologiesﻛﺸﻮر ﻛﺎﻧﺎدا( ﻣﻮرد ارزﻳﺎﺑﻲ ﻗﺮار ﮔﺮﻓﺘﻨﺪ.
ﺑﻪ ﺗﺮﺗﻴﺐ از ﻣﺨﻠﻮط اﺻﻠﻲ ) ،(Master Mix-Takaraآﻏﺎزﮔﺮ )5-Primer
ﻧﺘﺎﻳﺞ ﺑﻪدﺳﺖ آﻣﺪه در ﻧﺮماﻓﺰار SPSSوﻳﺮاﺳﺖ 16ﺑﺮرﺳﻲ ﺷﺪﻧﺪ و
ﭘﻴﻜﻮﻣﻮل( و 50) cDNAﻧﺎﻧﻮﮔﺮم( ﺑﻪ ﻣﻴﺰان ﺷﺶ ،ﻳﻚ و ﻳﻚ ﻣﻴﻜﺮوﻟﻴﺘﺮ
ﺑﺎ ﻛﻤﻚ P ،Student’s t-testﻣﺤﺎﺳﺒﻪ ﮔﺸﺖ و دادهﻫﺎ از ﻟﺤﺎظ ﻣﻌﻨﻲدار
را ﻣﺨﻠﻮط ﻛﺮده و ﺑﺎ آب ﻣﻘﻄﺮ ﺣﺠﻢ ﺑﻪ 12/5ﻣﻴﻜﺮوﻟﻴﺘﺮ رﺳـﺎﻧﺪه ﺷـﺪ.
ﺑﻮدن و ﻧﺒﻮدن ﺑﺮرﺳﻲ ﺷﺪﻧﺪ و ﻣﻘﺎدﻳﺮ P<0/05ﻣﻌﻨﻲدار ﻣﻲﺑﺎﺷﺪ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﺎ ﺗﻜﻨﻴﻚ RNAiدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز
90
ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ و در دو ﮔﺮوه ﺗﻴﻤﺎر ﺷﺪه ﺑـﺎ siRNAو ﻛﻨﺘـﺮل ﻣﻨﻔـﻲ
ﻳﺎﻓﺘﻪﻫﺎ
ﺷﻤﺎرش ﺷﺪﻧﺪ .اﻳﻦ ﺷـﻤﺎرش 48و 72ﺳـﺎﻋﺖ ﭘـﺲ از ﺗﺮاﻧﺴﻔﻜـﺸﻦ ﻛﺸﺖ ﺳﻠﻮلﻫﺎي :USSCﺳﻠﻮلﻫـﺎي USSCﭘـﺲ از ﺟﺪاﺳـﺎزي از
اﻧﺠﺎم ﮔﺸﺖ .ﻫﻤﺎنﻃﻮر ﻛﻪ اﺷﺎره ﺷﺪ ﺗﺮاﻧﺴﻔﻜﺸﻦ در روز ﺳﻮم ﭘﺲ از
ﺧﻮن ﺑﻨﺪﻧﺎف ﺑﻪ ﻣﺪت دو ﻫﻔﺘﻪ در ﻣﺤﻴﻂ ﻛﺸﺖ اﺧﺘـﺼﺎﺻﻲ ﻧﮕـﻪداري
ﺟﺪاﺳﺎزي اﻧﺠﺎم ﮔـﺸﺖ و ﺑﻌـﺪ از 48و 72ﺳـﺎﻋﺖ از زﻣـﺎن ﺗـﺮاﻧﺲ
ﺷﺪن ﺗﺎ ﻛﻠﻨﻲﻫﺎي اوﻟﻴﻪ ﺗﺸﻜﻴﻞ ﺷﻮﻧﺪ .اﻳﻦ ﺳﻠﻮلﻫـﺎ در اﺑﺘـﺪا ﺑـﻪ ﻓـﺮم
ﻓﻜﺸﻦ از ﻧﻈﺮ ﻣﻴـﺰان ﺑﻴـﺎن ﻧـﺴﺨﻪ (Transcript) RNAژن TGFbR2ﺑـﺎ
ﺳﺘﺎرهاي ﺷﻜﻞ ﻫﺴﺘﻨﺪ وﻟـﻲ ﭘـﺲ از رﺳـﻴﺪن ﺑـﻪ ﺗـﺮاﻛﻢ %80ﻛـﺸﻴﺪه،
اﺳﺘﻔﺎده از QRT-PCRارزﻳـﺎﺑﻲ ﺷـﺪﻧﺪ .در ﻧﻬﺎﻳـﺖ 96ﺳـﺎﻋﺖ ﭘـﺲ از
ﻣﻮازي و ﺗﺎ ﺣﺪودي دوﻛﻲ ﺷﻜﻞ ﺷﺪﻧﺪ )ﺷﻜﻞ -1ب( .اﻳﻦ ﺳـﻠﻮلﻫـﺎ
ﺗﺮاﻧﺴﻔﻜﺸﻦ ﺳﻠﻮلﻫﺎ از ﻧﻈﺮ اﻳﻤﻮﻧﻮﻓﻨﻮﺗﻴﭙﻲ ﺑﺎ ﻓﻠﻮﺳـﺎﻳﺘﻮﻣﺘﺮي و از ﻧﻈـﺮ
ﺑﺮاي ﭘﻮﺷﺎﻧﺪن ﺳﻄﺢ دارﺑﺴﺖ DBMو ﻫﻢﭼﻨﻴﻦ ﻛـﻒ ﭘﻠﻴـﺖ 48ﺧﺎﻧـﻪ
ﻋﻤﻠﻜﺮدي ﺑﺎ آزﻣﻮن ﻛﻠﻮﻧﻲزاﻳﻲ ﻣﻮرد ارزﻳﺎﺑﻲ ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﺑﻨﺎﺑﺮاﻳﻦ ﻛﻞ
ﺑﻪﻛﺎر ﺑﺮده ﺷﺪﻧﺪ .ﭘﺲ از رﺳﻴﺪن ﺑﻪ ﺗﺮاﻛﻢ ﻣﻨﺎﺳﺐ اﻳﻦ ﻻﻳﻪ ﺗﻐﺬﻳﻪ ﻛﻨﻨﺪه
روﻧﺪ ﺗﺰاﻳﺪ در ﻃﻲ ﻫﺸﺖ روز اﻧﺠﺎم ﮔﺸﺖ .ﺟﺪول 1ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ
)ﺳﻠﻮلﻫﺎي ﻓﻴﺪر (USSCﺑﺎ ﻣﻴﺘﻮﻣﺎﻳﺴﻴﻦ Cﻏﻴﺮ ﻓﻌﺎل ﮔﺸﺘﻨﺪ .ﭼﻨﺪ ﻗﻄﻌـﻪ
ﺑﻴﺶﺗﺮﻳﻦ ﺗﻌﺪاد ﺳﻠﻮل در ﮔﺮوه ﺗﻴﻤـﺎر ﺷـﺪه و در 72ﺳـﺎﻋﺖ ﭘـﺲ از
از دارﺑــﺴﺖ DBMﺣــﺎوي ﺳــﻠﻮلﻫــﺎي ﻓﻴــﺪر ﺑــﺮاي ﻋﻜــﺲﺑــﺮداري
ﺗﺮاﻧﺴﻔﻜﺸﻦ ﻣﺸﺎﻫﺪه ﺷﺪ .اﻳﻦ ﺗﺰاﻳﺪ در ﺣﺎﻟـﺖ ﻛـﺸﺖ روي ﻓﻴـﺪر ﺑـﻪ
ﻣﻴﻜﺮوﺳﻜﻮپ اﻟﻜﺘﺮوﻧﻲ روﺑﺸﻲ ) (SEMﺑﻪﻛﺎر رﻓﺘﻨـﺪ .ﺗـﺼﺎوﻳﺮ SEMاز
وﺿﻮح ﻗﺎﺑﻞ ﻣﺸﺎﻫﺪه ﺑﻮد.
DBM
آزﻣﻮن :QRT-PCRﺑﺮاي ﺳﻨﺠﺶ ﺗﻐﻴﻴﺮات اﻳﺠﺎد ﺷﺪه در ﻣﻴﺰان ﺑﻴﺎن
ﭘﻮﺷﻴﺪه ﺷﺪه از ﺳﻠﻮلﻫﺎي ﻓﻴﺪر ﺳـﻄﺤﻲ روﺷـﻦﺗـﺮ دارد و ﺳـﻠﻮلﻫـﺎ
ژن ﻣﻮرد ﻧﻈﺮ از آزﻣﻮن QRT-PCRاﺳﺘﻔﺎده ﺷﺪ .ﺑﻴﺎن ﻧﺴﺨﻪ RNAﺑـﺮاي
ﺑﻪﻃﻮر ﻣﺠﺰا ﺑﻪﺻﻮرت ﻧﻮارﻫﺎي ﻛﺸﻴﺪه و روﺷﻦ ﻗﺎﺑﻞ ﻣـﺸﺎﻫﺪه ﻫـﺴﺘﻨﺪ
ژن ﺑﺘــﺎ-اﻛﺘــﻴﻦ و ژن TGFbR2در دو ﮔــﺮوه ﻛﻨﺘــﺮل و ﺗﻴﻤــﺎر ﺷــﺪه ﺑــﺎ
)ﺷﻜﻞ .(1
SiRNAﺑﻌﺪ از 48و 72ﺳﺎﻋﺖ ارزﻳـﺎﺑﻲ ﺷـﺪ .ﻣﻴـﺰان ﻧـﺴﺒﺖ اﻳـﻦ دو
ﺳﻄﺢ دارﺑﺴﺖ DBMﺗﺨﻠﺨﻞ %40را ﻧﺸﺎن ﻣـﻲدﻫـﺪ .دارﺑـﺴﺖ
ﺗﺮاﻧﺴﻔﻜــﺸﻦ ﺳــﻠﻮلﻫــﺎي :CD34+ﺳــﻠﻮلﻫــﺎي CD34+ﺑــﺎ روش
روﻧﻮﺷﺖ ﺑﺎ روش Pfafflﻗﺎﻧﻮﻧﻤﻨﺪ ﺷﺪ .در ﻧﻬﺎﻳـﺖ ﻧﺘـﺎﻳﺞ ﺣـﺎﻛﻲ از آن
MACSاز ﺧﻮن ﺑﻨﺪﻧﺎف ﺟﺪاﺳﺎزي ﺷﺪﻧﺪ و ﺳﭙﺲ ﺑـﻪ ﺗﻌـﺪاد 30ﻫـﺰار
ﺑﻮد ﻛﻪ ﺑﺮاي ﻫﺮ ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ ،ﺑﻴﺶﺗﺮﻳﻦ ﻛﺎﻫﺶ ﺑﻴﺎن ژن ﺣﺪود 72
ﺳﻠﻮل در ﺳﻪ ﺣﺎﻟﺖ :ﻛﺸﺖ ﺳﺎده ،ﻛﺸﺖ روي ﻓﻴﺪر و ﻛﺸﺖ ﺳﻪ ﺑﻌﺪي
ﺳﺎﻋﺖ ﭘﺲ از ﺗﺮاﻧﺴﻔﻜﺸﻦ ﺣﺎﺻﻞ ﺑﻮده اﺳـﺖ .اﻣـﺎ در ﺑـﻴﻦ اﻳـﻦ ﺳـﻪ
ﺑﻪ ﭘﻠﻴـﺖ 48ﺧﺎﻧـﻪ اﺿـﺎﻓﻪ ﺷـﺪ .ﻣﺤـﻴﻂ ﺑـﻪﻛـﺎر رﻓﺘـﻪ ﻣﺤـﻴﻂ ﻛـﺸﺖ
ﺣﺎﻟﺖ ،ﺑﻴﺶﺗﺮﻳﻦ ﻛﺎﻫﺶ ﺑﻴﺎن ژن TGFbR2در ﻛﺸﺖ ﺳﺎده ﻣﺸﺎﻫﺪه ﺷﺪ
اﺧﺘﺼﺎﺻﻲ ﺳﻠﻮلﻫﺎي ﺑﻨﻴـﺎدي StemSpanﻫﻤـﺮاه ﺑـﺎ ﻓﺎﻛﺘﻮرﻫـﺎي ،SCF
ﻛﻪ در ﺣﺪود %51ﺑﻮد )ﻧﻤﻮدار .(1
™ Stealthﻋﻠﻴـﻪ TGFbR2و
ﺑﺮرﺳﻲ ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮﻳﻚ ﺳﻠﻮلﻫﺎي ﺗﺰاﻳـﺪ ﻳﺎﻓﺘـﻪ از ﻧﻈـﺮ ﻧـﺸﺎنﮔـﺮ
TPOو flt-3ﻣﻲﺑﺎﺷﺪ .ﻫﺮ ﺣﺎﻟﺖ ﺑﺎ
™ Stealthﺗﺮاﻧــﺴﻔﻜﺖ ﺷــﺪﻧﺪ .ﺑــﺮاي
:CD34در روز اول )روز ﺟﺪاﺳــﺎزي( و در روز ﻫــﺸﺘﻢ ﺳــﻠﻮلﻫــﺎي
BLOCK-iT TM alexa fluor
HSCsدر ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ و ﺑﺮاي ﻫﺮ ﺣﺎﻟﺖ در دو ﮔﺮوه ﺗﻴﻤـﺎر ﺷـﺪه
redاﺳﺘﻔﺎده ﺷﺪ .ﭘﺲ از ﺷﺶ ﺗﺎ ﻫﺸﺖ ﺳـﺎﻋﺖ از زﻣـﺎن ﺗﺮاﻧﺴﻔﻜـﺸﻦ،
ﺑﺎ siRNAﻋﻠﻴﻪ TGFbR2و ﻧﻴﺰ ﻛﻨﺘﺮل ،از ﻧﻈﺮ ﻣﻴﺰان ﻧـﺸﺎنﮔـﺮ ﺳـﻄﺤﻲ
ﻣﻴﺰان ﺗﺮاﻧﺴﻔﻜﺸﻦ در ﺳﻠﻮلﻫﺎي اﻳﻦ ﮔﺮوه ﺑﺎ اﺳﺘﻔﺎده از ﻣﻴﻜﺮوﺳﻜﻮپ
CD34ارزﻳﺎﺑﻲ ﺷﺪﻧﺪ .ﺗﻌﺪاد 100ﻫﺰار ﺳﻠﻮل ﺑﺮاي ﻫـﺮ ﮔـﺮوه ﺑﺮداﺷـﺖ
ﻓﻠﻮرﺳﺎﻧﺲ ﺑﺮرﺳﻲ ﺷﺪ .ﺑﻪ ﻃﻮر ﻣﻴﺎﻧﮕﻴﻦ ﻣﻴﺰان ﺗﺮاﻧﺴﻔﻜﺸﻦ ﺣﺪود %60
ﺷﺪ و ﭘﺲ از اﻧﻜﻮﺑﻪ ﺷﺪن ﺑﺎ آﻧﺘﻲﺑﺎدي ﻋﻠﻴﻪ ﻧـﺸﺎنﮔـﺮ CD34ﻧـﺸﺎندار
ﺗﺨﻤﻴﻦ زده ﺷﺪ )ﺷﻜﻞ .(2ﺗﺮاﻧﺴﻔﻜﺸﻦ روز ﺳـﻮم ﭘـﺲ از ﺟﺪاﺳـﺎزي
ﺷﺪه ﺑﺎ FITCو ﻫﻢﭼﻨﻴﻦ اﻳﺰوﺗﻴﭗ ﻛﻨﺘﺮل ،ﻧﺘﺎﻳﺞ ﻓﻠﻮﺳـﺎﻳﺘﻮﻣﺘﺮي ﻣﻄﺎﻟﻌـﻪ
ﺳﻠﻮلﻫﺎي CD34+اﻧﺠﺎم ﺷﺪ ﻛﻪ ﻋﻠﺖ اﻳﻦ ﻣﻮﺿﻮع ﻣﻘﺎوﻣﺖ ﺳﻠﻮلﻫﺎي
ﺷﺪﻧﺪ .ﺑﻪ ﻃﻮر ﻣﻴﺎﻧﮕﻴﻦ ﻣﻴﺰان ﺑﻴﺎن CD34در روز اول ﭘﺲ از ﺟﺪاﺳﺎزي
ﺧﻔﺘﻪ در ﺑﺮاﺑﺮ ﺗﺮاﻧﺴﻔﻜﺸﻦ اﺳﺖ .ﺑﻨﺎﺑﺮاﻳﻦ ﺑﺎ اﻟﻘﺎي رﺷﺪ در ﺳﻠﻮلﻫـﺎي
ﺣﺪود %89ﺑﻮد و در روز ﻫﺸﺘﻢ ﻣﻴﺰان ﺳﻠﻮلﻫﺎي CD34+در ﺟﻤﻌﻴـﺖ
ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﺑﺎ اﺳﺘﻔﺎده از ﻣﺤﻴﻂ ﻛﺸﺖ ازدﻳﺎد ﺳﻠﻮلﻫﺎي ﺑﻨﻴـﺎدي و
ﺳﻠﻮﻟﻲ اﻓﺖ ﻛﺮده و ﺑﻪ ﻣﻴﺰان 20/3 ،27/2و 14/1درﺻﺪ ﺑـﺮاي ﮔـﺮوه
در ﺣﻀﻮر ﺳﺎﻳﺘﻮﻛﻴﻦﻫﺎي اوﻟﻴﻪ ،ﺳﻠﻮلﻫـﺎي ﺧـﻮنﺳـﺎز اوﻟﻴـﻪ ﺑـﻴﺶﺗـﺮ
ﻛﻨﺘﺮل ﺑﻪ ﺗﺮﺗﻴﺐ در ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ ﺳﺎده ،ﻛﺸﺖ روي ﻓﻴﺪر و ﻛـﺸﺖ
ﻣﺴﺘﻌﺪ ﺗﺮاﻧﺴﻔﻜﺸﻦ ﺷﺪﻧﺪ.
روي DBMرﺳﻴﺪ .وﻟﻲ در ﮔﺮوه ﺗﻴﻤﺎر ﺷﺪه ﺑﺎ siRNAﻋﻠﻴـﻪ ،TGFbR2
ﻧﻴــﺰ
RNAi negative control
RNAi
ﺑﺮرﺳﻲ ﺑﺎزده و ﻛـﺎراﻳﻲ ﺗﺮاﻧﺴﻔﻜـﺸﻦ از
ﻧﺘﺎﻳﺞ ﺣﺎﺻﻞ از ﺷﻤﺎرش ﺳﻠﻮلﻫﺎي :CD34+ﺳﻠﻮلﻫﺎي CD34+در
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺣﺪود 30ﻫﺰار ﺳﻠﻮل ﺑﺎ آﻧﺎﻟﻴﺰ ﻓﻠﻮﺳﺎﻳﺘﻮﻣﺘﺮي %89اﺳﺘﻔﺎده ﺷـﺪ ،ﺗﻌﺪاد
زﻫﺮااﻟﺴﺎدات ﻫﺎﺷﻤﻲ و ﻫﻤﻜﺎران
91
ﺟﺪول :1 -ﺷﻤﺎرش ﺳﻠﻮلﻫﺎي CD34+در ﺣﺎﻻت و زﻣﺎنﻫﺎي ﻣﺨﺘﻠﻒ روز ﻗﺒﻞ از اﻧﺠﺎم
زﻣﺎن ﺣﺎﻟﺖ ﮔﺮوه
ﺗﻌﺪاد ﺳﻠﻮلﻫﺎ
ﻛﻨﺘﺮل
30×10
ﺗﺴﺖ
3
30×10
ﻛﻨﺘﺮل
3
30×10
ﺗﺴﺖ
3
30×10
ﻛﺸﺖ در ﺷﺮاﻳﻂ ﺳﻪ ﺑﻌـﺪي
ﻛﻨﺘﺮل
3
30×10
DBM
ﺗﺴﺖ
30×103
ﻛﺸﺖ روي ﻓﻴﺪر
48ﺳﺎﻋﺖ ﭘﺲ از ﺗﺮاﻧﺴﻔﻜﺸﻦ
ﺗﺮاﻧﺴﻔﻜﺸﻦ 3
ﻛﺸﺖ دو ﺑﻌﺪي ﺳﺎده
72ﺳﺎﻋﺖ ﭘﺲ از ﺗﺮاﻧﺴﻔﻜﺸﻦ
ﺗﻌﺪاد ﺳﻠﻮلﻫﺎ 3
(939)×10
ﺗﺰاﻳﺪ ﺳﻠﻮﻟﻲ 3/10/3
3
(16512)×10
3
(18915)×10
3
(29122)×10
3
(45017)×10
150/56
(71428)×103
23/80/9
5/50/42 6/30/51 9/70/74
ﺗﻌﺪاد ﺳﻠﻮلﻫﺎ
ﺗﺰاﻳﺪ ﺳﻠﻮﻟﻲ
3
7/050/25
(2117)×10
3
(43330)×10
3
(39012)×10
3
(66110)×10
3
(89219)×10
29/730/63
(123222)×103
41/060/73
14/451 12/990/4 22/040/86
ﺷﻜﻞ :1 -ﻋﻜﺲﺑﺮداري SEMاز ﺳﻄﺢ دارﺑﺴﺖ .DBMاﻟﻒ( ﺗﺼﻮﻳﺮ ﺳﻄﺢ دارﺑﺴﺖ DBMﺑﺎ ﻛﻤﻚ ﻣﻴﻜﺮوﺳﻜﻮپ SEMﺑﺪون ﺳﻠﻮلﻫﺎي ﻓﻴﺪر ﺑﻪ ﻋﻨﻮان ﻛﻨﺘﺮل .ب و ج( ﺗـﺼﻮﻳﺮ ﺳـﻄﺢ دارﺑـﺴﺖ DBMزﻣﺎﻧﻲ ﻛﻪ ﺑﺎ ﺳﻠﻮلﻫﺎي USSCﭘﻮﺷﺶ داده ﺷﺪه اﺳﺖ ﺑﺎ اﻧﺪازه اﺷﺎره ﺷﺪه در زﻳﺮ ﺷﻜﻞ ﻣﻲﺗﻮان ﺳﻠﻮلﻫﺎي USSCرا ﺑﻪﻃﻮر ﻣﺠﺰا ﻣﺸﺎﻫﺪه ﻛﺮد ﺣﺎل آنﻛﻪ در ﺗﺼﻮﻳﺮ اﻟﻒ ﺳﻠﻮﻟﻲ ﻣﺸﺎﻫﺪه ﻧﻤﻲﺷﻮد.
ﺳﻠﻮل CD34+در اﻳﻦ ﺟﻤﻌﻴﺖ ﺳﻠﻮﻟﻲ ﺑﻪدﺳـﺖ ﻣـﻲآﻳـﺪ ﻛـﻪ ﺑﺮاﺑـﺮ ﺑـﺎ ﺣﺪود 26700ﺳﻠﻮل اﺳﺖ .ﺑﻨﺎﺑﺮاﻳﻦ ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺟـﺪول ﺗﺰاﻳـﺪ ﺳـﻠﻮﻟﻲ )ﺟﺪول (2و ﻣﻴﺰان درﺻـﺪ ﻓﻠﻮﺳـﺎﻳﺘﻮﻣﺘﺮي ﺳـﻠﻮلﻫـﺎ در روز ﻫـﺸﺘﻢ، ﺗﺰاﻳﺪ ﺳﻠﻮﻟﻲ از ﻧﻈﺮ ﻓﻨﻮﺗﻴﭙﻲ ﺑﻪدﺳﺖ ﻣﻲآﻳﺪ )ﻧﻤﻮدار .(2 ﻧﺘﺎﻳﺞ ﺣﺎﺻﻞ از آزﻣﻮن ﻛﻠﻨﻲزاﻳﻲ :ﺑﺮاي ﺑﺮرﺳﻲ ﻋﻤﻠﻜﺮد ﺳﻠﻮلﻫﺎي ﺷﻜﻞ :2 -ﺳﻠﻮلﻫﺎي HSCsﺗﺮاﻧﺴﻔﻜﺖ ﺷـﺪه ﺑـﺎ
BLOCK-iT TM Alexa Fluor
HSCsاز آزﻣﻮن ﻛﻠﻨﻲزاﻳﻲ اﺳﺘﻔﺎده ﺷﺪ .ﺑﺪﻳﻦ ﺻﻮرت ﻛـﻪ ﺳـﻠﻮلﻫـﺎي
.Redاﻟﻒ( ﺗﺼﻮﻳﺮ ﺑﺎ اﺳﺘﻔﺎده از ﻧﻮر ﻣﺎوراي ﺑﻨﻔﺶ ﻣﻴﻜﺮوﺳﻜﻮپ ﻓﻠﻮرﺳﺎﻧﺲ .ب( ﺗﺼﻮﻳﺮ ﻫﻤـﻴﻦ
ﮔﺮوه ﻛﻨﺘﺮل و ﺗﻴﻤﺎر ﺷﺪه ﭘﺲ از ﻫﺸﺖ روز ﺗﺰاﻳﺪ ﺑﻪ ﻣﺪت دو ﻫﻔﺘﻪ در
ﺳﻠﻮلﻫﺎ ﺑﺎ ﻧﻮر ﻣﺮﺋﻲ ﻣﻴﻜﺮوﺳﻜﻮپ ﻓﻠﻮرﺳﺎﻧﺲ در ﻫﻤﺎن زﻣﻴﻨﻪ ﻗﺒﻠﻲ ﻛﻪ ﻧﺸﺎندﻫﻨﺪه ﻣﻮﻓﻘﻴـﺖآﻣﻴـﺰ
ﻣﺤﻴﻂ ﻧﻴﻤﻪ ﺟﺎﻣـﺪ ﻣﺘﻮﻛﺎﻟـﺖ ) (Methocultﻧﮕـﻪ داري ﺷـﺪﻧﺪ .ﺑﺮرﺳـﻲ
ﺑﻮدن ﺗﺮاﻧﺴﻔﻜﺸﻦ اﺳﺖ.
ﻛﻠﻨـﻲﻫﺎ ﻧﺸـﺎن داد ﻛـﻪ ﻛﻠﻨـﻲﻫﺎي ﻣﺘﻌﻠﻖ ﺑﻪ ﮔﺮوه آزﻣﻮن در ﻣﻘﺎﻳﺴﻪ ﺑـﺎ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻬﺎر ﻣﺴﻴﺮ TGF-bﺑﺎ ﺗﻜﻨﻴﻚ RNAiدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز
92
ﺗﺸﻜﻴﻞدﻫﻨﺪه ﻛﻠﻨﻲ دارد .در ﮔﺮوه آزﻣﻮن ﺑﻪﻃﻮر ﻣﻴـﺎﻧﮕﻴﻦ ﺑـﻪ ازاي ﻫـﺮ 1000ﺳﻠﻮل 90±15و در ﮔﺮوه ﻛﻨﺘﺮل 50±10ﻛﻠﻨﻲ ﺑﻪدﺳﺖ آﻣﺪ .ﺑﻴﻦ ﺳﻪ ﺣﺎﻟﺖ ﻛﺸﺖ ﺳﺎده ،روي ﻓﻴﺪر و DBMﺗﻔﺎوت ﻣﺤﺴﻮﺳﻲ ﻣـﺸﺎﻫﺪه ﻧﺸﺪ و ﺑﻪﻃﻮر ﻣﺘﻮﺳﻂ اﻳﻦ ﺗﻌﺪاد ﻛﻠﻨﻲ در ﮔﺮوه آزﻣﻮن و ﻛﻨﺘﺮل ﻫﺮ ﺳـﻪ ﺣﺎﻟﺖ ﺑﻪدﺳﺖ آﻣﺪ.
ﺑﺤﺚ ﺳﻠﻮلﻫﺎي USSCﺗﺤﺮﻳﻚ ﻧﺸﺪه ،در ﺣﺎﻟﺖ ﻃﺒﻴﻌﻲ ﻗﺎدر ﺑـﻪ ﺗﻮﻟﻴـﺪ ﻣـــﺸﺨﺺ ﺳـ ـﺎﻳﺘﻮﻛﻴﻦﻫـــﺎي ،CSF ،LIF ،TGF-1β ،M-CSF ،GM-CSF ،IL-15 ،IL-12 ،IL-11 ،IL-8 ،IL-6 ،IL-1β ،VEGF ﻧﻤﻮدار :1 -درﺻﺪ ﻛﺎﻫﺶ ﺑﻴـﺎن ژن TGFbR2در ﺳـﻠﻮلﻫـﺎي HSCsﺗﺮاﻧـﺴﻔﻜﺖ ﺷﺪه.
*.P<0/05
HGF ،SDF-1α
ﻣﻲﺑﺎﺷﻨﺪ .ﺳﻠﻮلﻫﺎي USSCﭼـﻪ در ﺣﺎﻟـﺖ ﺗﺤﺮﻳـﻚ ﻧـﺸﺪه و ﭼـﻪ در ﺣﺎﻟﺖ ﺗﺤﺮﻳﻚ ﺷﺪه ﺑﺎ IL-1βﻗﺎدر ﺑﻪ ﺗﻮﻟﻴﺪ FLt-3Lو TPOﻧﻴﺴﺘﻨﺪ وﻟﻲ G-SCFرا در ﻣﻘﺎدﻳﺮ ﻛﻢ ﻳﻌﻨﻲ 0/2pg/mlﺗﻮﻟﻴﺪ ﻣـﻲﻛﻨﻨـﺪ .ﺳـﻠﻮلﻫـﺎي USSCدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﺳﻠﻮلﻫـﺎي BM-MSCﺳـﻄﺢ ﺑـﺎﻻﺗﺮي از ،M-CSF IL-11 ،SDF-1α ،SCF ،LIF ،TGF-1βو ﺳــﻄﺢ ﭘــﺎﻳﻴﻦﺗــﺮي از ،VEGF IL-6 ،GM-CSFرا ﺗﻮﻟﻴﺪ ﻣـﻲﻛﻨﻨـﺪ .ﺳـﻠﻮلﻫـﺎي USSCدر ﻣﻘﺎﻳـﺴﻪ ﺑـﺎ ﺳﻠﻮلﻫﺎي ﻣﺰاﻧﺸﻴﻤﻲ ،ﺗﻠﻮﻣﺮاز ﺑﻠﻨﺪﺗﺮي دارﻧﺪ و ﺑﻨﺎﺑﺮاﻳﻦ ﻇﺮﻓﻴﺖ ﺑـﺎﻻﻳﻲ ﺑﺮاي ﺗﺰاﻳﺪ دارﻧﺪ .ﺳﻠﻮلﻫﺎي MSCدر ﭘﺎﺳﺎژﻫﺎي ﭘﺎﻳﻴﻦ ﺑﻪ ﺳﻤﺖ ﭘﻴـﺮي رﻓﺘﻪ و ﻗﺪرت ﺗﻜﺜﻴﺮ ﺧﻮد را از دﺳﺖ ﻣﻲدﻫﻨﺪ ﺣﺎل آنﻛـﻪ ﺳـﻠﻮلﻫـﺎي USSCدر ﭘﺎﺳﺎژﻫﺎي ﺑﺎﻻ ﻧﻴﺰ ﻫﻢﭼﻨﺎن ﺟﻮان ﻫﺴﺘﻨﺪ و ﺑـﻪ ﺳـﻤﺖ ﭘﻴـﺮي ﻧﻤﻲروﻧﺪ32.و 28-30زﻣﺎﻧﻲ ﻛﻪ ﺳﻠﻮلﻫﺎي ﻓﻴﺪر ﻣﺎﻧﻨﺪ ﻛـﺸﺖ دو ﺑﻌـﺪي از ﻳﻚ ﻃﺮف ﺑﻪ ﻛﻒ ﭘﻠﻴﺖ و از ﻃﺮف دﻳﮕﺮ ﺑﺎ ﺳﻠﻮلﻫﺎي ﻫﺪف در ﺗﻤﺎس ﺑﺎﺷﻨﺪ ،ﺗﻨﻬﺎ ﻗﺎدر ﺑﻪ ﺗﺮﺷﺢ ﻓﺎﻛﺘﻮرﻫﺎ در ﻳﻚ ﺳﻄﺢ ﻫﺴﺘﻨﺪ .اﻣﺎ زﻣﺎﻧﻲ ﻛـﻪ
ﻧﻤﻮدار :2 -ﻣﻴﺰان ازدﻳﺎد ﺳﻠﻮلﻫﺎي CD34ﺑﺮ اﺳﺎس ارزﻳﺎﺑﻲﻫﺎي اﻳﻤﻮﻧﻮﻓﻨﻮﺗﻴﭙﻲ در ﮔﺮوه آزﻣﻮن و ﻛﻨﺘﺮل.P<0/05* .
ﺳﻠﻮلﻫﺎي ﻓﻴﺪر در ﺳﻪ ﺑﻌﺪ ﺑﺎ ﻣﺤﻴﻂ در ﺗﻤﺎس ﺑﺎﺷﻨﺪ ،اﻓـﺰاﻳﺶ ﺗﺮﺷـﺢ ﻓﺎﻛﺘﻮرﻫﺎ را داﺷﺘﻪ و ﻣﻨﺠﺮ ﺑﻪ اﻓﺰاﻳﺶ ﻛﺎراﻳﻲ ﻓﻴﺪر ﻣﻲﺷﻮد ﺑﻪﻃﻮري ﻛـﻪ ﻏﻠﻈﺖ ﻓﺎﻛﺘﻮرﻫﺎ در اﻳﻦ ﻧﺎﺣﻴﻪ اﻓﺰاﻳﺶ ﻣﻲﻳﺎﺑﺪ .ﺳﻠﻮلﻫﺎي ﻓﻴﺪر واﺑـﺴﺘﻪ ﺑﻪ ﺳﻄﺢ ﻫﺴﺘﻨﺪ ﺑﻨﺎﺑﺮاﻳﻦ ﺑﺎ اﻓﺰاﻳﺶ ﻧﺴﺒﺖ ﺳﻄﺢ ﺑﻪ ﺣﺠﻢ اﺛﺮ ﺳﻠﻮلﻫﺎي
ﻣﻴﺰان CD34در ﺟﻤﻌﻴﺖ ﺑﻴﺶﺗﺮ ﺑﻮده و ﺑـﺮاي ﺳـﻪ ﺣﺎﻟـﺖ ﻣـﺬﻛﻮر ﺑـﻪ
ﻓﻴﺪر اﻓﺰاﻳﺶ ﻣﻲﻳﺎﺑﺪ .ﺗﺮﺷﺢ ﺑﻴﺶ از ﺣﺪ اﻳﻦ ﻓﺎﻛﺘﻮرﻫﺎ و ﻧﻴﺰ ﺗﻤـﺎس ﺑـﺎ
CD34
ﺳﻠﻮلﻫﺎي ﻓﻴﺪر ﻣﻨﺠﺮ ﺑﻪ ﺗﻤﺎﻳﺰ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز ﻣﻲﺷﻮد ﻛـﻪ
در ﮔﺮوه آزﻣﻮن ﻫﺮ ﺣﺎﻟﺖ ﻛﺸﺖ ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﻛﻨﺘﺮل ﻣﺮﺑﻮط ﺑﻪ ﻫﻤﺎن
اﻳﻦ ﺳﻠﻮلﻫـﺎي CD34+در اﻳـﻦ ﺣﺎﻟـﺖ دﻳﮕـﺮ ﺟﻤﻌﻴﺘـﻲ ﻧـﺎﻫﻤﮕﻮن از
ﺣﺎﻟﺖ ،ﻧﺸﺎندﻫﻨﺪه ﺗﺄﺛﻴﺮ ﻣﻬﺎر ﻋﻼﻣﺖدﻫﻲ TGF-bﺑﺮ ﻣﻴـﺰان ﺑـﺮوز اﻳـﻦ
ﺳﻠﻮلﻫﺎي ﺧﻮﻧﻲ ﻣﻲﺑﺎﺷـﻨﺪ ﻛـﻪ ﻣﺎرﻛﺮﻫـﺎي ﺳـﻄﺤﻲ ﻣﺨﺘﻠﻔـﻲ را ﺑﻴـﺎن
ﻧﺸﺎنﮔﺮ ﺳﻄﺤﻲ اﺳﺖ .ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ اﻳـﻦ ﻛـﻪ در روز اول آزﻣـﺎﻳﺶ در
ﻣﻲﻛﻨﻨﺪ .ﻫﺮ ﻳﻚ از اﻳﻦ ﺳﻠﻮلﻫﺎ در ﻳﻚ ﻣﺮﺣﻠﻪ ﺗﻤﺎﻳﺰي ﻫﺴﺘﻨﺪ ﻛﻪ اﻳـﻦ
ﮔﺮوه ﻛﻨﺘﺮل اﻧﺪازه ﺑﺰرگﺗﺮي داﺷﺘﻨﺪ ﻛﻪ ﻧﺸﺎن از اوﻟﻴﻪ ﺑﻮدن ﺳﻠﻮلﻫﺎي
ﺳﻠﻮلﻫﺎ ﻣﻲﺗﻮاﻧﻨﺪ ﺳﻠﻮل ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز اوﻟﻴﻪ ﺗﺎ ﺳﻠﻮل ﻣﺮﺑﻮط ﺑـﻪ رده
ﺗﺮﺗﻴﺐ 24/7 ،32/6و 17/5درﺻﺪ ﻣﺸﺎﻫﺪه ﺷﺪ .اﻓﺰاﻳﺶ ﻣﻴـﺰان
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻫﻤﻜﺎران ﻫﺎﺷﻤﻲ و زﻫﺮااﻟﺴﺎدات Hashemi Z.S. et al.
93
ﺧﺎص ﺑﺎﺷﻨﺪ .ﺑﻨﺎﺑﺮاﻳﻦ در اﻃﺮاف ﺳﻠﻮلﻫـﺎي ﻓﻴـﺪر ﻏﻠﻈـﺖ ﻛـﺎﻧﻮﻧﻲ از
ﮔﺮوه آزﻣﻮن ﺑﻪ ﮔﺮوه ﻛﻨﺘـﺮل در ﺣﺎﻟـﺖ ﻛـﺸﺖ دو ﺑﻌـﺪي ﺳـﺎده 2/46
ﻓﺎﻛﺘﻮرﻫﺎ و ﭘﺮوﺗﻴﻴﻦﻫﺎي ﻣﺨﺘﻠﻒ اﺳـﺖ ﻛـﻪ ﺑﺎﻋـﺚ درﮔﻴـﺮي و اﻳﺠـﺎد
ﺧﻮاﻫﺪ ﺑﻮد ﺣﺎل آنﻛﻪ در ﻛﺸﺖ روي ﻓﻴﺪر اﻳﻦ ﻋﺪد 2/06و در ﻛﺸﺖ
ﺳﻄﺢ ﭼﺴﺒﻨﺪه ﺑﺮاي ﺳﻠﻮلﻫﺎي HSCﻣﻲﻛﻨﺪ .در ﺣﺎﻟﺖ ﺳﻪ ﺑﻌـﺪي اﻳـﻦ
ﺳﻪ ﺑﻌﺪي DBMﺑﻪ 1/71رﺳﻴﺪه اﺳﺖ .ﺑﺮرﺳﻲ ﻣﺎرﻛﺮ ﺳﻄﺤﻲ ﻧﻴﺰ ﻧﺸﺎن
ﺗﺮاﻛﻢ ﺑﻴﺶ از دو ﺑﻌﺪي ﻫﻤﺮاه ﺑﺎ ﻓﻴﺪر اﺳﺖ .ﺳﻠﻮلﻫﺎي CD34+ﻛـﻪ در
داد ﻛﻪ اﻓﺰاﻳﺶ ﺑﻴﺎن ﻣﺎرﻛﺮ CD34در ﮔﺮوه ﺗﻴﻤﺎر ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﻛﻨﺘـﺮل
ﻧﺰدﻳﻚ ﺳﻠﻮلﻫﺎي USSCﻗـﺮار دارﻧـﺪ ﺗﺤـﺖ ﺗـﺎﺛﻴﺮ ﻣـﺎﺗﺮﻳﻜﺲ ﺧـﺎرج
در ﺣﺎﻟﺖ دو ﺑﻌﺪي ﺳﺎده %5/4و در ﺣﺎﻟﺖ ﺳـﻪ ﺑﻌـﺪي %3/4ﺑـﻮد .در
ﺳﻠﻮﻟﻲ اﻳﻦ ﺳﻠﻮلﻫﺎ ﻫﺴﺘﻨﺪ و آزادي ﻛﺎﻓﻲ در ﺳﻪ ﺑﻌﺪ را ﻧﺪارﻧﺪ .زﻣﺎﻧﻲ
ﻧﻬﺎﻳﺖ ﺑﺎ اﻧﺠﺎم Real time PCRﻣﻴﺰان ﻛﺎﻫﺶ ﺑﻴﺎن ژن ﺑـﻪﻃـﻮر ﺧـﺎﻟﺺ
ﻛﻪ اﻟﻴﮕﻮﻧﻮﻛﻠﺌﻮﺗﻴـﺪ ﺗـﺪاﺧﻠﻲ ) (siRNAوارد اﻳـﻦ ﻣﺤـﻴﻂ ﻣـﻲﺷـﻮد در
ﺑﻪدﺳﺖ آﻣﺪ ﻛﻪ در اﻳﻦﺟﺎ ﻧﻴﺰ ﻧﺸﺎن از ﺑﻴﺶﺗﺮﻳﻦ ﻛﺎﻫﺶ ﺑﻴﺎن در ﻛـﺸﺖ
اﻃﺮاف ﺳﻠﻮلﻫﺎي CD34+ﺷـﻨﺎور ﻣـﻲﺑﺎﺷـﻨﺪ ﺗـﺎ ﺑـﺎ ﻛﻤـﻚ ﻛﻤـﭙﻠﻜﺲ
دو ﺑﻌﺪي ﺳﺎده داﺷﺖ .اﻳﻦ ﻧﺘﺎﻳﺞ ﻧـﺸﺎندﻫﻨـﺪه ﻣـﻮﺛﺮﺗﺮ ﺑـﻮدن ﺳﻴـﺴﺘﻢ
ﻟﻴﭙﻮﻓﻜﺘــﺎﻣﻴﻦ وارد ﺳــﻠﻮلﻫــﺎ ﺷــﻮﻧﺪ .در اﻳــﻦ ﺣﺎﻟــﺖ ﺑــﺮاي ورود ﺑــﻪ
اﻧﺘﻘﺎل و ﺗﺤﻮﻳﻞ siRNAدر ﻣﺤﻴﻂ دو ﺑﻌﺪي ﺳـﺎده دارد ﺑـﻪﻃـﻮري ﻛـﻪ
ﺳﻠﻮلﻫﺎي ﺧﻮنﺳﺎز ﺑﺎﻳﺪ از ﺳﻪ ﺑﻌﺪ ﻛﻤﻚ ﺑﮕﻴﺮد ﺗـﺎ اﻧﺘﻘـﺎل ﺳـﻠﻮﻟﻲ ﺑـﺎ
ﺳﻠﻮلﻫﺎ در ﺳﻪ ﺑﻌﺪ آزاد ﺑﺎﺷﻨﺪ و ﻣﻨﺎﻓﺬ آنﻫﺎ ﺑﺮاي ورود siRNAﺑﻴﺶﺗﺮ
ﻛﺎراﻳﻲ ﺑﻬﺘﺮ اﻧﺠﺎم ﺷﻮد .ﺑﺮاي ﺳﻠﻮلﻫـﺎي ﺧـﻮنﺳـﺎز ﻛـﻪ ﺗﺤـﺖ ﺗـﺎﺛﻴﺮ
در دﺳﺘﺮس ﺑﺎﺷﻨﺪ .اﻳﻦ ﺳﻠﻮلﻫﺎي دﺳﺖورزي ﺷﺪه ﺑﺎ siRNAﻋﻠﻴﻪ ژن
ﺳﻠﻮلﻫﺎي ﻓﻴﺪر ﻫـﺴﺘﻨﺪ اﻳـﻦ اﻟﻴﮕﻮﻧﻮﻛﻠﺌﻮﺗﻴـﺪ ﺑﺎﻳـﺪ از ﺳـﺪ ﻣـﺎﺗﺮﻳﻜﺲ
TGFbR2ﻗﺎﺑﻞ اﺳﺘﻔﺎده در ﻓﺎز ﺑﺎﻟﻴﻨﻲ ﻣﻲﺑﺎﺷـﻨﺪ زﻳـﺮا اﻳـﻦ دﺳـﺖورزي
ﺳﻠﻮﻟﻲ ﻋﺒﻮر ﻛﻨﺪ ﻛﻪ اﺣﺘﻤـﺎل ﺗﻤـﺎس و دﺳﺘﺮﺳـﻲ آن ﺑـﻪ ﺳـﻠﻮلﻫـﺎي
ﺑﻪﺻﻮرت ﻣﻮﻗﺖ ﻣـﻲﺑﺎﺷـﺪ و siRNAدر ﺣـﺪاﻛﺜﺮ 72ﺳـﺎﻋﺖ ﭘـﺲ از
ﺧﻮنﺳﺎز ﻛﺎﻫﺶ ﻣﻲﻳﺎﺑﺪ و ﺑﺴﻴﺎري از siRNAﻫﺎ ﺑﻪ ﺳـﻠﻮلﻫـﺎي ﻫـﺪف
ﺗﺮاﻧﺴﻔﻜﺸﻦ از ﻣﺤﻴﻂ ﺣﺬف ﻣﻲﺷﻮد و اﻳﻦ ﺗﻴﻤـﺎر ﺑـﻪﺻـﻮرت داﻳﻤـﻲ
وارد ﻧﻤﻲﺷﻮﻧﺪ و در ﻧﻬﺎﻳﺖ ﻧـﺸﺎن از ﻛـﺎﻫﺶ ﻛـﺎراﻳﻲ ﺳﻴـﺴﺘﻢ اﻧﺘﻘـﺎل
ﻧﻤﻲﺑﺎﺷﺪ .زﻳﺮا ﻣﺴﻴﺮ TGFbدر ﺑﺴﻴﺎري از ﻣـﺴﻴﺮﻫﺎي ﺳـﻠﻮﻟﻲ دﺧﺎﻟـﺖ
) (siRNA deliveryدر ﺣﺎﻟﺖ ﺳﻪ ﺑﻌﺪي ﻣﻲﺑﺎﺷﺪ .ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺟـﺪول 1
داﺷﺘﻪ و ﭘﻴﺎمﻫﺎي ﺣﺴﺎس ﺳﻠﻮﻟﻲ ﺑﺎ اﻳﻦ ﻓﺎﻛﺘﻮر ﻣﻨﺘﻘﻞ ﻣـﻲﺷـﻮد .ﻫـﺪف
ﻣﺸﺎﻫﺪه ﻣﻲﺷﻮد ﻛﻪ ﻧﺴﺒﺖ ﺗﺰاﻳﺪ ﺳﻠﻮﻟﻲ در ﺣﺎﻟـﺖ ﺳـﺎده در دو ﮔـﺮوه
ﻧﻬﺎﻳﻲ ﺗﺰاﻳﺪ ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧﻮنﺳﺎز اﺳـﺘﻔﺎده آنﻫـﺎ در ﭘﻴﻮﻧـﺪ ﻣﻐـﺰ
ﻛﻨﺘﺮل و آزﻣﻮن ﺑﺮاﺑﺮ ﺑﺎ 2/04ﻣﻲﺑﺎﺷـﺪ } {14/45÷7/05 =2/04ﻳﻌﻨـﻲ
اﺳﺘﺨﻮان اﺳﺖ.
در ﺣﺎﻟﺖ ﺳﺎده ﮔﺮوه ﺗﻴﻤﺎر ﺷﺪه ﻧﺴﺒﺖ ﺑﻪ ﻛﻨﺘـﺮل ﺧـﻮد در ﺣـﺪود دو
ﺳﭙﺎﺳﮕﺰاري :اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﺑﺨﺸﻲ از ﭘﺎﻳـﺎنﻧﺎﻣـﻪ ﺗﺤـﺖ ﻋﻨـﻮان
ﺑﺮاﺑﺮ اﻓﺰاﻳﺶ ﺗﻌﺪاد داﺷﺘﻪ اﺳﺖ ﺣﺎل آنﻛﻪ اﻳﻦ ﻧـﺴﺒﺖ در ﻛـﺸﺖ روي
"ﺑﺮرﺳﻲ ﻣﻬﺎر ﺑﻴﺎن ژن TGF-βدر ﺳﻠﻮلﻫﺎي ﺑﻨﻴﺎدي ﺧـﻮن ﺑﻨـﺪﻧﺎف ﺑـﺮ
ﻓﻴﺪر 1/69و ﻛﺸﺖ روي DBMﺑﻪ 1/38ﻛﺎﻫﺶ ﻳﺎﻓﺘﻪ اﺳﺖ .ﺑـﺎ ﺗﻮﺟـﻪ
روي دارﺑــﺴﺖ ﺳــﻪ ﺑﻌــﺪي MBAﺟﻬــﺖ اﻓــﺰاﻳﺶ ﺧــﻮدﺗﻜﺜﻴﺮي اﻳــﻦ
ﺑﻪ ﻧﺘﺎﻳﺞ ،اﻓﺰاﻳﺶ ﻓﻨﻮﺗﻴﭙﻲ در ﮔﺮوه ﺗﻴﻤﺎر ﺷﺪه ﻛﺸﺖ دو ﺑﻌـﺪي ﺳـﺎده،
ﺳﻠﻮلﻫﺎ" در ﻣﻘﻄﻊ ﻛﺎرﺷﻨﺎﺳﻲ ارﺷﺪ در ﺳـﺎل 1389و ﻛـﺪ 1017637
5/28و ﮔﺮوه ﻛﻨﺘﺮل 2/14ﻣﻲﺑﺎﺷﺪ ﺑﻨـﺎﺑﺮاﻳﻦ ﻧـﺴﺒﺖ اﻓـﺰاﻳﺶ ﻓﻨـﻮﺗﻴﭙﻲ
ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﺑﺎ ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﺪرس اﺟﺮا ﺷﺪه اﺳﺖ.
References 6.
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TGF-b downregulation by RNAi technique in ex vivo-expanded HSCs on 3D DBM scaffold
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22. Sitnicka E, Ruscetti FW, Priestley GV, Wolf NS, Bartelmez SH. Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells. Blood 1996;88(1):82-8. 23. Ramsfjell V, Borge OJ, Cui L, Jacobsen SE. Thrombopoietin directly and potently stimulates multilineage growth and progenitor cell expansion from primitive (CD34+ CD38-) human bone marrow progenitor cells: distinct and key interactions with the ligands for ckit and flt3, and inhibitory effects of TGF-beta and TNF-alpha. J Immunol 1997;158(11):5169-77. 24. Keller JR, Mcniece IK, Sill KT, Ellingsworth LR, Quesenberry PJ, Sing GK, et al. Transforming growth factor beta directly regulates primitive murine hematopoietic cell proliferation. Blood 1990;75(3):596-602. 25. Pierelli L, Marone M, Bonanno G, Mozzetti S, Rutella S, Morosetti R, et al. Modulation of bcl-2 and p27 in human primitive proliferating hematopoietic progenitors by autocrine TGF-beta1 is a cell cycle-independent effect and influences their hematopoietic potential. Blood 2000;95(10):3001-9. 26. Yamazaki S, Iwama A, Takayanagi S, Eto K, Ema H, Nakauchi H. TGF-beta as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation. Blood 2009;113(6):1250-6. 27. Larsson J, Blank U, Klintman J, Magnusson M, Karlsson S. Quiescence of hematopoietic stem cells and maintenance of the stem cell pool is not dependent on TGF-beta signaling in vivo. Exp Hematol 2005;33(5):592-6. 28. Kögler G, Sensken S, Wernet P. Comparative generation and characterization of pluripotent unrestricted somatic stem cells with mesenchymal stem cells from human cord blood. Exp Hematol 2006;34(11):1589-95. 29. Kögler G, Somville T, Göbel U, Hakenberg P, Knipper A, Fischer J, et al. Haematopoietic transplant potential of unrelated and related cord blood: the first six years of the EUROCORD/NETCORD Bank Germany. Klin Padiatr 1999;211(4):224-32. 30. Kogler G, Callejas J, Hakenberg P, Enczmann J, Adams O, Daubener W, et al. Hematopoietic transplant potential of unrelated cord blood: critical issues. J Hematother 1996;5(2):105-16. 31. Tomasz M. Mitomycin C: small, fast and deadly (but very selective). Chem Biol 1995;2(9):575-9. 32. Kögler G, Radke TF, Lefort A, Sensken S, Fischer J, Sorg RV, et al. Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 2005;33(5):573-83.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
95
ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺑﺮاي2,ﭘﺎﻳﺶ روش ﻛﺎراﻳﻲ دو Tehran University Medical Journal; Vol.ﺗﺸﺨﻴﺺ 70, No. May 2012: 86-95
TGF-b downregulation by RNAi technique in ex vivo-
expanded HSCs on 3D DBM scaffold
Abstract Zahra Sadat Hashemi M.Sc.1 Mahdi Forouzandeh Moghadam Ph.D.1* Masoud Soleimani Ph.D.2 Maryam Hafizi M.Sc.3 Naser Amirizadeh Ph.D.4 1- Department of Biotechnology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran. 2- Department of Hematology and Blood Banking, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran. 3- Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran. 4- Research Center of Iranian Blood Transfusion Organization, Tehran, Iran.
Received: November 22, 2011 Accepted: February 05, 2012
Background: Bone Marrow Transplantations (BMT) are limited by low CD34+ cell counts in umbilical cord blood (UCB) and these cells need to be expanded for success in such procedures. To achieve this goal, ex vivo expansion of hematopoietic stem cells (HSCs) by enhancing their self-renewal activity on demineralized bone matrix (DBM) scaffold coated with mesenchymal progenitor cells (MPCs) and unrestricted somatic stem cells (USSCs) was recommended. TGF-b pathway is a key inhibitory factor for HSCs self-renewal. In this study ex vivo expansion and downregulation of TGF-b
pathway were simultaneously performed. Methods: USSC cells were isolated from UCB and then coated on DBM scaffold as a feeder layer. UCB CD34+ cells were isolated from UCB by magnetic activated cell sorting (MACS) method and were transfected by siRNA against TGFbR2 in twodimensional (2D) and three-dimensional (3D) cultures by co-cultivation with USSC. TGFbR2 expression levels were evaluated by quantitative real-time PCR. Cell count and
flow cytometry were performed and clonogenic activity was evaluated. Results: Ex vivo expansion of CD34+ cells was significantly enhanced (41±0.7 folds) by TGFbR2 downregulation, especially in 2D than 3D cultures. Finally, 2D culture showed
less TGFbR2 expression levels and higher increase in the percentage of CD34 markers by flow cytometry assay. Conclusion: The 3D siRNA delivery system would be of lower efficiency in contrast to 2D settings where the cells have less freedom and are in more contact with the feeder
layer. Keywords: Demineralized bone matrix, scaffold, hematopoietic stem cells, siRNA, TGF*
Corresponding author: Department of Biotechnology, Tarbiat Modares University, Medical Faculty, Intersection of Chamran and AL-E-Ahmad Highways P.O. Box: 14115-111, Tehran, Iran. Tel: +98- 21- 82883861 E-mail: foroz@modares.ac.ir
beta pathway.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
دﻫﺎﻧ-ﻲ96 ﺲ103 ،1391 ﺷﻤﺎره ،2 اﻓﺮاد ، 70 ﺗﻬﺮان،ازدوره ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎهيﻋﻠﻮم اردﻳﺒﻬﺸﺖﺪﻳﺎزﻳ ﻣﺒﺘﻼ ﺑﻪ ﻛﺎﻧﺪﻳ HIVﻣﺜﺒﺖ ﺟﺪاﺷﺪه ﻛﺎﻧﺪﻳﺪاي ﭘﺰﺷﻜﻲ ،ﮔﻮﻧﻪﻫﺎ داﻧﺸﻜﺪهﺣﺴﺎﺳﻴﺖ ﻣﺠﻠﻪﺑﺮرﺳﻲ
96
ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي دﻫﺎﻧﻲ اﻓﺮاد آﻟﻮده ﺑﻪ HIVﻧﺴﺒﺖ ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﺗﺤﺖ ﺷﺮاﻳﻂ ﺑﺮون ﺗﻨﻲ در اﻳﺮان
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/09/17 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/01 :
ﭼﻜﻴﺪه
ﻓﺮزاد ﻛﺘﻴﺮاﺋﻲ *1،ﻋﻠﻴﺮﺿﺎ ﺧﺴﺮوي،
2 4
وﺣﻴﺪ ﺧﻠﺞ 3،ﻣﺤﺒﻮﺑﻪ ﺣﺎﺟﻲ ﻋﺒﺪاﻟﺒﺎﻗﻲ،
4
ﻋﻠﻲاﺻﻐﺮ ﺧﺎﻛﺴﺎر 3،ﻣﻬﺮﻧﺎز رﺳﻮﻟﻲ ﻧﮋاد
زﻣﻴﻨﻪ و ﻫﺪف :ﻣﻘﺎوﻣﺖ ﻋﻮاﻣﻞ اﻳﺠﺎد ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ از ﻣﺸﻜﻼت ﺑﻴﻤﺎران آﻟـﻮده ﺑـﻪ
HIV
اﺳﺖ .اﻓﺰاﻳﺶ ﻣﻘﺎوﻣﺖ و اﺳﺘﻔﺎده ﺑﻴﺶ از ﭘﻴﺶ از داروﻫﺎ ،اﻫﻤﻴﺖ ﺑﺮرﺳﻲ ﺣﺴﺎﺳﻴﺖ آﻧﺘـﻲﺑﻴـﻮﺗﻴﻜﻲ را ﻧـﺸﺎن ﻣـﻲدﻫـﺪ. -1ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻗﺎرچﺷﻨﺎﺳﻲ ،داﻧﺸﻜﺪه ﻋﻠﻮم
ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷﺪه از ﺑﻴﻤﺎران آﻟـﻮده ﺑـﻪ HIVرا ﺑـﻪ داروﻫـﺎي ﺿـﺪ ﻗـﺎرﭼﻲ
داﻣﭙﺰﺷﻜﻲ ،داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ واﺣﺪ ﻋﻠﻮم و
ﺑﺮرﺳﻲ ﻣﻲﻛﻨﺪ .روش ﺑﺮرﺳﻲ 150 :ﻧﻤﻮﻧﻪ دﻫﺎﻧﻲ از ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ HIVﺑﺮ روي ﻣﺤﻴﻂﻫﺎي ﻛﺮوم آﮔﺎر و ﺳﺎﺑﻮرو آﮔﺎر
ﺗﺤﻘﻴﻘﺎت ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان. -2ﮔﺮوه ﻣﻴﻜﺮوﺑﻴﻮﻟﻮژي ،داﻧﺸﻜﺪه داﻣﭙﺰﺷﻜﻲ،
ﻛﺸﺖ داده ﺷﺪ .ﺟﺪاﻳﻪﻫﺎي رﺷﺪ ﻳﺎﻓﺘﻪ ﺑﺮ اﺳﺎس روشﻫﺎي ﻣﺘﺪاول ﺗﺸﺨﻴﺺ ﻣﺨﻤﺮﻫﺎ ﺗﻌﻴﻴﻦ ﻫﻮﻳﺖ ﺷﺪﻧﺪ .ﺑﺎ روشﻫﺎي
داﻧﺸﮕﺎه ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان.
اﻧﺘﺸﺎر دﻳﺴﻚ و ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث اﻟﮕﻮي ﺣﺴﺎﺳﻴﺖ ﺑﻪ ﺷﺶ داروي ﺿﺪ ﻗﺎرﭼﻲ ﺗﻌﻴﻴﻦ ﮔﺮدﻳـﺪ .ﻳﺎﻓﺘـﻪﻫـﺎ :ﻛﺎﻧﺪﻳـﺪا
-3ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﺑﻴﻮﺗﻜﻨﻮﻟﻮژي ،اﻧﺴﺘﻴﺘﻮ ﭘﺎﺳﺘﻮر
آﻟﺒﻴﻜﻨﺲ ) (%50/2و ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ) (%22ﺷﺎﻳﻊﺗﺮﻳﻦ ﮔﻮﻧﻪﻫـﺎي ﺟـﺪا ﺷـﺪه ﺑﻮدﻧـﺪ %25/7 .از ﺟﺪاﻳـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪا
اﻳﺮان. -4ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت اﻳﺪز اﻳﺮان ،ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎم
آﻟﺒﻴﻜﻨﺲ ﻧﺴﺒﺖ ﺑﻪ داروي ﻓﻠﻮﻛﻮﻧﺎزول ﻣﻘﺎوم ﺑﻮدﻧﺪ و اﻳﻦ ﻣﻴﺰان ﺑﺮاي ﻛﺘﻮﻛﻮﻧﺎزول و ﻛﻠﻮﺗﺮﻳﻤﺎزول ﺑـﻪ ﺗﺮﺗﻴـﺐ %21/9و
ﺧﻤﻴﻨﻲ )ره( ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان،
%16/4ﺑﻮده اﺳﺖ .ﻣﻘﺎوﻣﺖ ﻧﺴﺒﺖ ﺑﻪ داروﻫﺎي آﻣﻔﻮﺗﺮﻳـﺴﻴﻦ ،ﻧﻴـﺴﺘﺎﺗﻴﻦ و داروي ﻛﺎﺳـﭙﻮﻓﺎﻧﮋﻳﻦ دﻳـﺪه ﻧـﺸﺪ .از ﻃﺮﻓـﻲ
اﻳﺮان.
%57/7از ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻧﺴﺒﺖ ﺑﻪ ﻓﻠﻮﻛﻮﻧﺎزول ﻣﻘﺎوم ﺑﻮدﻧﺪ و اﻳﻦ ﻣﻴﺰان ﺑﺮاي ﻛﺘﻮﻛﻮﻧﺎزول و ﻛﻠﻮﺗﺮﻳﻤﺎزول ﺑﻪ ﺗﺮﺗﻴﺐ %31و %35ﺑـﻮد .ﻧﺘﻴﺠﻪﮔﻴﺮي :ﻣﻘﺎوﻣـﺖ ﮔﻮﻧـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪا ﺑـﻪ داروي آزوﻟـﻲ ،ﺑـﻪﺧـﺼﻮص ﻓﻠﻮﻛﻮﻧـﺎزول رو ﺑﻪ اﻓﺰاﻳﺶ اﺳﺖ .ﺑﺮرﺳﻲ ﻣﻘﺎوﻣـﺖ ﺟﺪاﻳـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪا ﺑـﻪروش اﻧﺘـﺸﺎر دﻳـﺴﻚ و ﻳـﺎ ﻣﻴﻜﺮوداﻳﻠﻮﺷـﻦ ﺑـﺮاث در آزﻣﺎﻳﺸﮕﺎهﻫﺎ ﺟﻬﺖ ﻛﻨﺘﺮل ﻋﻔﻮﻧﺖ ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ﻣﻄﻠﻮب اﺳﺖ .ﻫﺮﭼﻨﺪ داروي ﻧﻴﺴﺘﺎﺗﻴﻦ ﺑﻪوﻓـﻮر ﺑـﺮاي ﺑﻴﻤـﺎران
*
ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻗﺎرچﺷﻨﺎﺳﻲ داﻧﺸﮕﺎه
آزاد اﺳﻼﻣﻲ واﺣﺪ ﻋﻠﻮم و ﺗﺤﻘﻴﻘﺎت ﺗﻬﺮان ،ﺑﺎﻻﺗﺮ از ﻣﻴﺪان ﺳﺮو ،ﻧﺮﺳﻴﺪه ﺑﻪ ﻓﺮوﺷﮕﺎه ﺷﻬﺮوﻧﺪ ،ﻧﺒﺶ ﻓﺮاز ﻳﻜﻢ
ﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﻣﻲﮔﻴﺮد اﻣﺎ ﻣﻘﺎوﻣﺖ ﺑﻪ اﻳﻦ دارو ﻧﺎﭼﻴﺰ اﺳﺖ .اﺳﺘﻔﺎده از داروي ﻛﺎﺳﭙﻮﻓﺎﻧﮋﻳﻦ ﻧﻴﺰ ﺑـﺎ ﺗﻮﺟـﻪ ﺑـﻪ ﻋـﺪم ﻣﻘﺎوﻣﺖ ﺗﻮﺻﻴﻪ ﻣﻲﮔﺮدد.
ﺗﻠﻔﻦ0912-6047311 : E-mail: katiraee_f@yahoo.com
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ،ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ،ﻣﻘﺎوﻣﺖ داروﻳﻲ ،ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ .HIV
ﻣﻘﺪﻣﻪ
ﺣﺎوي ﻣﻘﺎدﻳﺮ اﻧﺪﻛﻲ از ﮔﻮﻧﻪﻫﺎي ﻣﺨﻤﺮي ﺑﻪ ﺻﻮرت ﻫﻢزﻳﺴﺖ اﺳـﺖ و اﻟﺒﺘﻪ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاﻳﻲ ﺑﻪ ﻃﻮر ﻣﻌﻤﻮل ﺣﻔﺮه دﻫـﺎﻧﻲ ﺑﻴﻤـﺎران
HIV
اﻫﻤﻴﺖ ﺑﻴﻤﺎريﻫﺎي ﻗﺎرﭼﻲ ﻓﺮﺻـﺖ ﻃﻠـﺐ در ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ ﺑـﻪ
را ﺑﻴﺶ از ﺣﺪ ﻃﺒﻴﻌﻲ ﻛﻮﻟﻮﻧﻴﺰه ﻣﻲﻛﻨﻨﺪ ﻛﻪ ﺧﻮد از ﻋﻮاﻣﻞ ﻣﺴﺘﻌﺪ ﻛﻨﻨﺪه
ﻧﻘﺎﻳﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ و ﺧـﺼﻮﺻﺎ اﻳﻤﻨـﻲ ﺳـﻠﻮﻟﻲ ﺑـﺮ ﻛـﺴﻲ ﭘﻮﺷـﻴﺪه
ﺑﺮاي اﻳﺠﺎد ﺑﻴﻤﺎري ﻛﺎﻧﺪﻳﺪاﻳﻲ اﺳﺖ .اﻣﺮوزه از ﻣﺸﻜﻼت اﺻـﻠﻲ در راه
ﻧﻴﺴﺖ .ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ) (Oral candidiasisراﻳـﺞﺗـﺮﻳﻦ ﻋﻔﻮﻧـﺖ
درﻣﺎن ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻋﻔﻮﻧﺖﻫﺎي ﻗـﺎرﭼﻲ و ﺧـﺼﻮﺻﺎ ﺑﻴﻤـﺎريﻫـﺎي
ﻗﺎرﭼﻲ ﻓﺮﺻﺖ ﻃﻠﺐ در ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ وﻳﺮوس ﻧﻘﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨـﻲ
ﻛﺎﻧﺪﻳﺪاﻳﻲ ﺑﺮوز ﻣﻘﺎوﻣﺖﻫﺎي داروﻳﻲ اﺳﺖ و ﻫﻤﺎنﻃﻮر ﻛـﻪ ﻣـﻲداﻧﻴـﺪ
اﺳﺖ و از ﻃﺮﻓﻲ ﺑﻴﻤﺎريﻫﺎي ﻛﺎﻧﺪﻳﺪاﻳﻲ ﺷﺎﻳﻊﺗﺮﻳﻦ ﻋﻔﻮﻧﺖ ﻗـﺎرﭼﻲ در
درﻣﺎن ﻋﻔﻮﻧﺖﻫﺎي ﻗﺎرﭼﻲ ﺑﻪ دﻟﻴﻞ ﻃﻮل ﻣﺪت درﻣﺎن ،ﻋﻮد ﻣﻜﺮر ،ﻋـﺪم
اﻧﺴﺎن و ﺣﻴﻮان ﻧﻴـﺰ ﻣـﻲﺑﺎﺷـﻨﺪ و اﻳـﻦ اﻫﻤﻴـﺖ ﺑﺮرﺳـﻲ ﺑـﺮ روي اﻳـﻦ
4و3
وﺟﻮد ﺗﻨﻮع در اﻧﺘﺨﺎب داروﻫﺎي ﻣﺨﺘﻠﻒ ﺑﻪﻃﻮر اوﻟﻴﻪ ﻣﺸﻜﻞ اﺳـﺖ.
ﮔﻮﻧﻪﻫﺎي ﻗﺎرﭼـﻲ را ﻧﺸـﺎن ﻣـﻲدﻫـﺪ2.و 1ﺣﻔـﺮه دﻫﺎﻧﻲ اﻧﺴﺎن و ﺣﻴﻮان
ازدﻳﺎد ﮔﺰارشﻫﺎي ﻣﺨﺘﻠﻒ و ﻣﺘﻔﺎوت از ﺳﺮاﺳﺮ دﻧﻴﺎ در راﺑﻄﻪ ﺑﺎ ﺑـﺮوز
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻓﺮزاد ﻛﺘﻴﺮاﺋﻲ و ﻫﻤﻜﺎران
97
و اﻓﺰاﻳﺶ ﻣﻘﺎوﻣﺖﻫﺎي داروﻳﻲ در ﺑﻴﻦ ﮔﻮﻧﻪﻫﺎي ﻗـﺎرﭼﻲ و ﻛﺎﻧﺪﻳـﺪاﻳﻲ
ﺑﻴﻤﺎريﻫﺎي رﻓﺘﺎري واﻗﻊ در ﺑﻴﻤﺎرﺳـﺘﺎن اﻣـﺎم ﺧﻤﻴﻨـﻲ ﺗﻬـﺮان در ﺳـﺎل
و ﻫﻢﭼﻨﻴﻦ ﻛﻤﻚ و ﺗﻬﻴﻴﺞ ﭘﺰﺷﻜﺎن ﺑـﻪ ﺗﺠـﻮﻳﺰ داروي ﻣﻨﺎﺳـﺐ و ﻛـﺎرا
1387ﺑﻪدﺳﺖ آﻣﺪهاﻧﺪ .ﻋﻔﻮﻧﺖ ﺑﻴﻤﺎران ﺑﻪ وﻳﺮوس HIVﺑﺎ روش اﻻﻳﺰا
ﺑﺮاي ﺑﻴﻤﺎران ،و در ﻛﻨﺎر آن ﺗﻮﻟﻴﺪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﺟﺪﻳﺪ ﻧﻴـﺎز ﺑـﻪ
و وﺳﺘﺮن ﺑﻼت ﺑﻪ ﺗﺎﻳﻴﺪ رﺳﻴﺪه ﺑﻮد و ﺑﻴﻤﺎران داراي ﭘﺮوﻧﺪه ﭘﺰﺷﻜﻲ در
اﻧﺠﺎم آزﻣﺎﻳﺶﻫـﺎي ﺗﻌﻴـﻴﻦ ﺣـﺴﺎﺳﻴﺖ را ﺑـﻪ داروﻫـﺎي ﻣـﺬﻛﻮر ﻧـﺸﺎن
راﺑﻄﻪ ﺑﺎ ﻋﻔﻮﻧﺖ HIVﺑﻮدهاﻧﺪ .ﺿﺎﻳﻌﺎت دﻫﺎﻧﻲ در ﻛﻠﻴﻪ ﺑﻴﻤـﺎران از ﻧﻈـﺮ
ﻣﻲدﻫﺪ و ﻣﺤﻘﻘﺎن را ﻣﺸﺘﺎق ﺑﻪ ﺗﻌﻴﻴﻦ اﻟﮕﻮي ﺣـﺴﺎﺳﻴﺖ ﺑـﻪ داروﻫـﺎي
ﺑﺎﻟﻴﻨﻲ ﺑﺮرﺳﻲ ﺷﺪ و از ﻫﺮ ﺑﻴﻤﺎر ﻧﻤﻮﻧﻪ ﺳﻮاب دﻫﺎﻧﻲ از ﻧـﻮاﺣﻲ ﻣﺨـﺎط
5
ﻣﺨﺘﻠﻒ ﺿﺪ ﻗﺎرﭼﻲ ﻣﻲﻛﻨﺪ.
دﻫﺎن ،زﺑﺎن و ﻟﺜﻪ در ﻣﺤﻴﻂ ﺳﺎﺑﻮرو دﻛﺴﺘﺮوز آﮔـﺎر ) (Merckو ﻣﺤـﻴﻂ
ﺑﺎ وﺟﻮد درﻣﺎن وﺳﻴﻊ ﺿﺪ ﻗﺎرﭼﻲ و درﻣﺎن ﺿﺪ وﻳﺮوﺳﻲ ﻣﻮﺛﺮ ﻛـﻪ
ﻛﺮوم آﮔﺎر ﻛﺎﻧﺪﻳﺪا ) (Paris France companyﺑﻪﻃـﻮر ﻣـﺴﺘﻘﻴﻢ ﻛـﺸﺖ
ﻣﻨﺠﺮ ﺑـﻪ ﺑﻬﺒـﻮد ﺳﻴـﺴﺘﻢ اﻳﻤﻨـﻲ در ﺑﻴﻤـﺎران HIVﻣـﻲﮔـﺮدد ،ﺑﻴﻤـﺎري
داده ﺷﺪ .ﻫﻢﭼﻨﻴﻦ ﻧﻤﻮﻧـﻪ دﻫـﺎﻧﻲ ﺑـﺎ اﺳـﺘﻔﺎده از ﭘﺘـﺎس %10ﺑـﻪروش
ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ در اﻳﻦ ﺑﻴﻤﺎران راﻳـﺞ اﺳـﺖ و اﻟﺒﺘـﻪ ﻣﻴـﺰان ﺑـﺮوز
ﻣﻴﻜﺮوﺳﻜﻮﭘﻲ از ﻧﻈﺮ وﺟﻮد ﻫﺎﻳﻒ ﻛﺎذب و ﺳﻠﻮلﻫﺎي ﻣﺨﻤﺮي ﺑﺮرﺳﻲ
ﺑﻴﻤﺎري واﺑﺴﺘﻪ ﺑﻪ ﮔﻮﻧﻪ ﻋﺎﻣﻞ اﻳﺠﺎد ﺑﻴﻤﺎري ،ﺷـﻴﻮع ﻣﻘﺎوﻣـﺖ داروﻳـﻲ،
ﺷﺪﻧﺪ .ﭘﻠﻴﺖﻫﺎي ﻛﺸﺘﻪ داده ﺷﺪه ﻛﺮوم آﮔﺎر ﺑـﺮاي ﺗـﺸﺨﻴﺺ اﺣﺘﻤـﺎﻟﻲ
درﻣﺎن ﻗﺒﻠﻲ ﺑﺎ داروي ﺿﺪ ﻗﺎرﭼﻲ و ﺷﺮاﻳﻂ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ ﻣﻴﺰﺑـﺎن دارد.
ﮔﻮﻧﻪﻫﺎي ﻣﺨﻤﺮي و ﺷﻜﻞ و رﻧﮓ ﻛﻠﻨﻲ ﺑﻪﻣﺪت 72ﺳـﺎﻋﺖ در دﻣـﺎي º
ﻣﻄﺎﻟﻌﺎت ﻣﺨﺘﻠﻔﻲ ﺑﺮ روي ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪاي ﺟـﺪا
C
ﺷﺪه از ﺑﻴﻤﺎران HIVدر ﺳﺮاﺳﺮ دﻧﻴﺎ اﻧﺠﺎم ﺷﺪه اﺳﺖ اﻣﺎ ﻣﻴـﺰان ﺷـﻴﻮع
در ﺷﺮاﻳﻂ ﻫﻮازي ﺑﻪﻣﺪت ﻫﻔﺖ روز در دﻣﺎي
ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﻣﻘﺎوم ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ در ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ
ﺗﺎ ﺗﻤﺎم ﻋﻮاﻣﻞ اﺣﺘﻤﺎﻟﻲ در اﻳﻦ ﻣﺤﻴﻂ رﺷﺪ ﻳﺎﺑﻨـﺪ .ﭘـﺲ از ﻃـﻲ زﻣـﺎن
HIVدر اﻳﺮان ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﻧﮕﺮﻓﺘﻪ اﺳﺖ .ﭘﺮ واﺿﺢ اﺳـﺖ ﺗﻌﻴـﻴﻦ
اﻧﻜﻮﺑﺎﺳﻴﻮن ﮔﻮﻧﻪﻫﺎي ﻣﺨﻤﺮي ﺑﺎ روشﻫﺎي ﻣﺨﺘﻠﻒ از ﺟﻤﻠـﻪ ﺗـﺸﻜﻴﻞ
اﻟﮕﻮي ﺣﺴﺎﺳﻴﺖ ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﮔﻮﻧـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪاي ﺟـﺪا
ﻛﻼﻣﻴﺪوﺳﭙﻮر در ﻣﺤﻴﻂ ﻛﻮرن ﻣﻴﻞ آﮔـﺎر ﺣـﺎوي ﺗـﻮﻳﻴﻦ 80و ﺟـﺬب
ﺷﺪه از ﺑﻴﻤﺎران ﻧﻘـﺺ اﻳﻤﻨـﻲ و از ﺟﻤﻠـﻪ ﺑﻴﻤـﺎران آﻟـﻮده ﺑـﻪ HIVدر
)(Rap IDTM yeast identification system remel
ﭘﻴﺸﮕﻴﺮي و درﻣﺎن ﺻﺤﻴﺢ اﻳﻦ ﺑﻴﻤﺎران ﻣـﻮﺛﺮ و اﺳﺎﺳـﻲ اﺳـﺖ .ﺗﻌﻴـﻴﻦ
35و در ﺗﺎرﻳﻜﻲ اﻧﻜﻮﺑﻪ ﺷﺪﻧﺪ و ﭘﻠﻴﺖﻫﺎي ﺳﺎﺑﻮرو دﻛـﺴﺘﺮوز آﮔـﺎر
ﻛﺮﺑﻮﻫﻴـﺪراتﻫـﺎ
C
º
30اﻧﻜﻮﺑﻪ ﮔﺮدﻳﺪﻧـﺪ
10-13
ﺷﻨﺎﺳﺎﻳﻲ ﺷﺪﻧﺪ.
ﺣﺴﺎﺳﻴﺖ ﺑﻪ روش اﻧﺘﺸﺎر دﻳﺴﻚ ﻛﻪ ﻳﻚ روش ﺳﺎده و ﭘﺬﻳﺮﻓﺘﻪ ﺷـﺪه
-آزﻣﺎﻳﺶ ﺗﻌﻴﻴﻦ ﺣﺴﺎﺳﻴﺖ ﺑﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ
در آزﻣﺎﻳﺸﮕﺎهﻫﺎ اﺳﺖ ﺟﻬﺖ ﺗﻌﻴﻴﻦ ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪا ﺑـﻪ
روش اﻧﺘﺸﺎر دﻳﺴﻚ :اﻳﻦ روش ﺑﺮاي ﭘﻨﺞ داروي ﺿﺪ ﻗـﺎرﭼﻲ ﺑـﺮ
داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﺑﻪ ﺧﻮﺑﻲ اراﻳﻪ ﺷﺪه و ﮔﺴﺘﺮش ﻳﺎﻓﺘﻪ اﺳـﺖ و ﺑـﺎ
Clinical and Laboratory Standards
اﺳــﺎس روش ﭘﻴــﺸﻨﻬﺎدي
Instituteﺗﺤﺖ ﻋﻨﻮان M44-Aاﻧﺠﺎم ﮔﺮﻓﺖ15.و 14ﺑﺪﻳﻦ ﻣﻨﻈـﻮر
وﺟﻮد آنﻛﻪ در ﺗﻌﻴﻴﻦ دﻗﻴﻖ ﻣﻘﺎوﻣﺖ ﺑﻪ دارو ﺑﺎ ﻣﺸﻜﻼﺗﻲ ﻣﻮاﺟﻪ ﻫﺴﺘﻴﻢ
)(CLSI
اﻣﺎ ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ روش اﻧﺘﺸﺎر دﻳﺴﻚ ﻳﻚ روش ﺳـﺎده و ﺑـﻪ ﻧـﺴﺒﺖ
دﻳﺴﻚﻫﺎي آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ ﻓﻠﻮﻛﻮﻧـﺎزول ) ،(25µgﻛﺘﻮﻛﻮﻧـﺎزول )،(15µg
ارزان ﺑﺮاي آزﻣﺎﻳﺶ ﺗﻌﻴﻴﻦ ﺣﺴﺎﺳﻴﺖ در آزﻣﺎﻳﺸﮕﺎهﻫﺎي ﺑﺎﻟﻴﻨﻲ ﻣﺨﺘﻠـﻒ
ﻛﻠﻮﺗﺮﻳﻤــﺎزول ) ،(10µgﻧﻴــﺴﺘﺎﺗﻴﻦ ) (50µgو آﻣﻔﻮﺗﺮﻳــﺴﻴﻦ (10µg) B
اﺳﺖ 6-9.ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷـﺪه
ﺗﻬﻴﻪ و ﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﮔﺮﻓﺖ ) .(Mast group Ltd, UKاز دو ﺳـﻮﻳﻪ
از ﺑﻴﻤﺎران آﻟﻮده ﺑـﻪ HIVرا ﺑـﻪ ﺑﺮﺧـﻲ داروﻫـﺎي ﺿـﺪ ﻗـﺎرﭼﻲ ﻧـﺸﺎن
اﺳﺘﺎﻧﺪارد ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ) (ATCC1023و ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ
(CD
ﻣﻲدﻫﺪ و در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺟﻬﺖ ﺗﻌﻴﻴﻦ ﻫﺮ ﭼﻪ ﺑﻬﺘﺮ ﻣﻴﺰان ﻣﻘﺎوﻣﺖ از دو
) 36در ﻛﻨﺎر ﺳﺎﻳﺮ ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاﻳﻲ ﺑﻪﻛﺎر ﺑﺮده ﺷﺪه در اﻳﻦ ﻣﻄﺎﻟﻌـﻪ
روش اﻧﺘﺸﺎر دﻳﺴﻚ و ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث اﺳﺘﻔﺎده ﺷﺪه اﺳﺖ.
ﺑﻪﻋﻨﻮان ﻛﻨﺘﺮل اﺳﺘﻔﺎده ﺷﺪ .ﭘﻠﻴﺖﻫﺎي ﻣﻮﻟﺮ ﻫﻴﻨﺘﻮن آﮔﺎر ) (MHAﺣﺎوي %2ﮔﻠــﻮﻛﺰ و ﻣﺘـﻴﻠﻦ ﺑﻠـﻮ ) (GMBﺑــﺎ ﻗﻄــﺮ ﭼﻬــﺎر ﻣﻴﻠـﻲﻣﺘــﺮ ﺑــﺮ ﻃﺒــﻖ
روش ﺑﺮرﺳﻲ
دﺳــﺘﻮراﻟﻌﻤﻞ ﺷــﺮﻛﺖ ﺳــﺎزﻧﺪه ﺗﻬﻴ ـﻪ و ﻣــﻮرد اﺳــﺘﻔﺎده ﻗــﺮار ﮔﺮﻓــﺖ. ﺳﻮﺳﭙﺎﻧﺴﻴﻮن ﺳﻠﻮلﻫﺎي ﻣﺨﻤﺮي در ﺳﺮم ﻓﻴﺰﻳﻮﻟﻮژي اﺳﺘﺮﻳﻞ ﻣﻄﺎﺑﻖ ﺑـﺎ
اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﺗﻮﺻﻴﻔﻲ -ﺗﺤﻠﻴﻠﻲ اﺳـﺖ .در اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ
ﻛﺪورت ﻧﻴﻢ ﻣﻚ ﻓﺎرﻟﻨـﺪ )ﻛـﻪ ﺣـﺎوي 1-5×106ﺳـﻠﻮل اﺳـﺖ( ﺗﻬﻴـﻪ
ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺑﻪﻛﺎر رﻓﺘﻪ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ از 150ﺑﻴﻤـﺎر
ﮔﺮدﻳﺪ .ﺳﭙﺲ ﺳﻄﺢ ﻣﺤﻴﻂ ﻛﺸﺖ آﻣﺎده ﺷﺪه ﺑﻪوﺳﻴﻠﻪ ﺳـﻮآب اﺳـﺘﺮﻳﻞ
آﻟﻮده ﺑﻪ وﻳﺮوس ﻧﻘﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ ﻣﺮاﺟﻌﻪ ﻛﻨﻨﺪه ﺑـﻪ ﻣﺮﻛـﺰ ﻣـﺸﺎوره
آﻏﺸﺘﻪ ﺷﺪه ﺑﻪ ﺳﻮﺳﭙﺎﻧﺴﻴﻮن ﺳﻠﻮلﻫﺎي ﻣﺨﻤﺮي ﺗﺎزه ﻛـﺸﺖ داده ﺷـﺪه
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺑﺮرﺳﻲ ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪاﺷﺪه از اﻓﺮاد HIVﻣﺜﺒﺖ ﻣﺒﺘﻼ ﺑﻪ ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ
98
ﺗﻠﻘﻴﺢ ﮔﺮدﻳﺪ .ﭘﻠﻴﺖﻫﺎي ﺗﻠﻘﻴﺢ ﺷﺪه ﺑﻪﻣﺪت 24و 48ﺳﺎﻋﺖ در دﻣـﺎي 35 ºCاﻧﻜﻮﺑﻪ ﮔﺮدﻳﺪﻧﺪ .ﻗﻄﺮ ﻫﺎﻟﻪ ﻋﺪم رﺷﺪ از ﻧﻘﻄﻪاي ﻛﻪ رﺷﺪ ﻣﺨﻤـﺮ
ﻳﺎﻓﺘﻪﻫﺎ
MICﮔﻮﻧﻪﻫﺎي
ﺑــﺮ اﺳــﺎس ﺟــﺪول 1ﻛﺎﻧﺪﻳـﺪا آﻟﺒﻴﻜــﻨﺲ ) (%50/2و ﺑـﻪدﻧﺒــﺎل آن
ﻣﺨﻤﺮي ﻣﺘﻨﺎﺳﺐ ﺑﺎ ﻗﻄﺮ ﻫﺎﻟﻪ ﻋﺪم رﺷﺪ و ﺑﺮ اﺳﺎس ﻣﻌﻴﺎر ﺗﻮﺻﻴﻒ ﺷﺪه
ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ) (%22ﺷﺎﻳﻊﺗﺮﻳﻦ ﮔﻮﻧﻪﻫﺎي ﺟﺪا ﺷﺪه از ﺣﻔﺮه دﻫـﺎﻧﻲ
از ﻃﺮف CLSIو ﺷﺮﻛﺖ ﺳﺎزﻧﺪه دﻳﺴﻚﻫـﺎي آﻧﺘـﻲﺑﻴـﻮﺗﻴﻜﻲ ﻣﺤﺎﺳـﺒﻪ
ﺑﻴﻤــﺎران آﻟــﻮده ﺑــﻪ وﻳـﺮوس HIVﺑﻮدﻧــﺪ .در راﺑﻄــﻪ ﺑــﺎ ﻣﻴـﺰان ﺷـﻴﻮع
ﮔﺮدﻳﺪ.
ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ و اﺷﻜﺎل ﺑـﺎﻟﻴﻨﻲ ﻣﺨﺘﻠـﻒ آن در اﻳـﻦ ﺑﻴﻤـﺎران در
ﺑﻪ ﻣﻴﺰان %80ﻛﺎﺳﺘﻪ ﺷﺪه ﺑﻮد ﻣﺤﺎﺳﺒﻪ ﮔﺮدﻳﺪ .ﺳﭙﺲ
90
19
روش ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث :در ﻛﻨـﺎر روش اﻧﺘـﺸﺎر دﻳـﺴﻚ و ﺑـﺎ
ﻣﻘﺎﻟﻪ دﻳﮕﺮي ﺑﻪ ﺗﻔﺼﻴﻞ ﭘﺮداﺧﺘﻪاﻳﻢ .دوﻳﺴﺖ ﺟﺪاﻳﻪ ﻛﺎﻧﺪﻳـﺪا از ﻧﻈـﺮ
ﻫﺪف ﻣﻘﺎﻳﺴﻪ و ﺗﺎﻳﻴﺪ از روش رﻗﺖﺳﺎزي ﺳﺮﻳﺎﻟﻲ در ﻣﺤـﻴﻂ ﻣـﺎﻳﻊ در
ﺣﺴﺎﺳﻴﺖ ﺑﻪ ﭘﻨﺞ داروي ﺿﺪ ﻗﺎرﭼﻲ ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﺟﺪول
ﻣﻴﻜﺮوﭘﻠﻴﺖﻫﺎي 96ﺧﺎﻧـﻪاي ﺑـﺮ ﻃﺒـﻖ روش ﭘﻴـﺸﻨﻬﺎدي CLSIﺗﺤـﺖ
2ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﻣﻮرد ﺑﺮرﺳـﻲ را ﺑـﻪ داروﻫـﺎي
ﻋﻨﻮان M27-A2اﺳﺘﻔﺎده ﮔﺮدﻳﺪ 16.در اﻳـﻦ روش ﺑـﺎ اﺳـﺘﻔﺎده از ﻣﺤـﻴﻂ
ﻛﻠﻮﺗﺮﻳﻤﺎزول ،ﻛﺘﻮﻛﻮﻧـﺎزول ،ﻛﻠﻮﺗﺮﻳﻤـﺎزول ،آﻣﻔﻮﺗﺮﻳـﺴﻴﻦ ،ﻧﻴـﺴﺘﺎﺗﻴﻦ و
pH:7
ﻛﺎﺳﭙﻮﻓﺎﻧﮋﻳﻦ را ﻧﺸﺎن ﻣﻲدﻫﺪ .ﺑﺮ اﺳﺎس روش اﻧﺘـﺸﺎر دﻳـﺴﻚ از 105
ﺣﺪاﻗﻞ ﻏﻠﻈﺖ ﻣﻬﺎري ﺗﻌﻴﻴﻦ ﮔﺮدﻳﺪ .در اﺑﺘﺪا ﻏﻠﻈﺖﻫﺎي اﺳـﺘﻮك ﭘـﻨﺞ
ﺟﺪاﻳﻪ ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻣﻮرد ﺑﺮرﺳﻲ %25/7ﺑﻪ ﻓﻠﻮﻛﻮﻧـﺎزول ﻣﻘﺎوﻣـﺖ
داروي ﻣﻮرد ﻧﻈﺮ ﺑـﺮ ﻃﺒـﻖ دﺳـﺘﻮراﻟﻌﻤﻞ CLSIدر ﻣﺤـﻴﻂ RPMIﺗﻬﻴـﻪ
ﻧﺸﺎن دادﻧﺪ ) ،(MIC≥64µg/mlﻫـﻢﭼﻨـﻴﻦ %21/9و %16/4از ﻛﺎﻧﺪﻳـﺪا
ﮔﺮدﻳﺪ و در ﻫﻨﮕﺎم آزﻣﺎﻳﺶ در ﭼﺎﻫﻚﻫﺎي ﭘﻠﻴﺖ 96ﺧﺎﻧﻪاي ﺑﺎ اﺳﺘﻔﺎده
آﻟﺒﻴﻜﻨﺲﻫﺎي ﻣﻮرد ﺑﺮرﺳﻲ ﺑﻪ ﺗﺮﺗﻴﺐ ﺑـﻪ ﻛﺘﻮﻛﻮﻧـﺎزول و ﻛﻠﻮﺗﺮﻳﻤـﺎزول
از ﻣﺤﻴﻂ RPMIﺑﻪ رﻗﺖ ﻣﻮرد ﻧﻈﺮ رﺳـﺎﻧﺪه ﺷـﺪ .در ﻛﻨـﺎر رﻗـﺖﻫـﺎي
ﻣﻘﺎوﻣــﺖ ﻧــﺸﺎن دادﻧــﺪ ) .(MIC>0/125µg/mlﻣﻘــﺎدﻳﺮ MIC-%90و
ﺳﺮﻳﺎﻟﻲ ﺗﻬﻴﻪ ﺷﺪه از دو ﭼﺎﻫـﻚ ﺑـﺮاي ﻛﻨﺘـﺮل ﻣﺜﺒـﺖ و ﻛﻨﺘـﺮل ﻣﻨﻔـﻲ
ﻣﺤﺪوده MICﺑﻪدﺳﺖ آﻣﺪه ﺑﻪروش ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث ﺑـﺮاي ﺳـﺎﻳﺮ
اﺳﺘﻔﺎده ﺷﺪ .ﺳﻮﺳﭙﺎﻧﺴﻴﻮن ﺳـﻠﻮلﻫـﺎي ﻣﺨﻤـﺮي در ﺳـﺮم ﻓﻴﺰﻳﻮﻟـﻮژي
ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ﻣﻮرد ﺑﺮرﺳﻲ در ﺟﺪول 2ﻧﺸـﺎن داده ﺷـﺪه اﺳـﺖ.
RPMI1640
ﺣﺎوي ﮔﻠﻮﺗﺎﻣﻴﻦ و ﮔﻠﻮﻛﺰ ﺑـﻪ ﻫﻤـﺮاه ﺑـﺎﻓﺮ MOPSﺑـﺎ
اﺳﺘﺮﻳﻞ ﺑﺎ اﺳﺘﻔﺎده از ﺳﻠﻮلﻫﺎي ﻣﺨﻤﺮي ﺗﺎزه ﻛﺸﺖ داده ﺷﺪه در ﻣﺤﻴﻂ SDAآﻣﺎده ﺷﺪ و ﺑﻪ ﻣﻴﺰاﻧﻲ از آن ﺑﺮداﺷﺖ ﮔﺮدﻳﺪ ﻛﻪ ﭘﺲ از اﻓﺰودن آن ﺑﻪ ﭼﺎﻫﻚﻫﺎي ﻣﻴﻜﺮوﭘﻠﻴﺖ 96ﺧﺎﻧـﻪاي ﺣـﺎوي ﻣﺤـﻴﻂ ﻛـﺸﺖ و دارو ﺷﻤﺎرش ﻧﻬﺎﻳﻲ آن در ﻣﺤﺪوده 0/5-2/5×103/mlﻗﺮار ﮔﻴﺮد .ﭘﻠﻴﺖﻫﺎي
ﺟﺪول :1 -ﻓﺮاواﻧﻲ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷﺪه از ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ ﮔﻮﻧﻪﻫﺎ
HIV
ﻓﺮاواﻧﻲ
درﺻﺪ
ك .آﻟﺒﻴﻜﻨﺲ
103
50/2
ﻣﺠﺪدا ﻛﺸﺖ داده ﺷﺪﻧﺪ و ﺑﻪﻣﺪت 24ﺳﺎﻋﺖ در دﻣﺎي 35 ºCاﻧﻜﻮﺑـﻪ
ك .ﮔﻼﺑﺮاﺗﺎ
45
22
ك.داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ
9
4/4
ﮔﺮدﻳﺪﻧﺪ .ﺣﺪاﻗﻞ ﻏﻠﻈﺖ داروي ﺿﺪ ﻗﺎرﭼﻲ ﻛﻪ ﺑﻪ ﻣﻴﺰان %90ﻣـﺎﻧﻊ از
ك .ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ
7
3/4
رﺷﺪ ﻗﺎرچ در ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﭼﺎﻫﻚ ﻛﻨﺘـﺮل ﻣﺜﺒـﺖ ﺷـﺪه ﺑﺎﺷـﺪ ﺑـﻪ ﻋﻨـﻮان
ك .ﻛﻔﻴﺮ
7
3/4
MIC90ﺗﻠﻘﻲ ﻣﻲﮔﺮدد .ﻣﻼك ﺣـﺴﺎﺳﻴﺖ ﻳـﺎ ﻣﻘﺎوﻣـﺖ ﺑـﺮاي ﺑﺮﺧـﻲ از
ك .ﭘﺎراﭘﺴﻠﻴﻮزﻳﺲ
6
2/9
ك .ﻓﺎﻣﺎﺗﺎ
2
1/0
ك .ﮔﻠﻴﺮﻣﻮﻧﺪي
1
0/5
ك .ﻛﺮوزهاي
1
0/5
واﺑﺴﺘﻪ ﺑﻪ دوز و 64µg/ml≥MICﺑﻪ ﻋﻨﻮان ﻣﻘﺎوم ﺷﻨﺎﺧﺘﻪ ﻣـﻲﺷـﻮد .در
ﺳﺎﻛﺎروﻣﺎﻳﺴﺲ
2
1/0
راﺑﻄﻪ ﺑﻪ ﻛﺘﻮﻛﻮﻧـﺎزول و ﻛﻠﻮﺗﺮﻳﻤـﺎزول 0/125µg/ml>MICﺑـﻪ ﻋﻨـﻮان
ﺗﺮﻳﻜﻮﺳﭙﻮرون
2
1/0
ﺣﺴﺎس ﺷﻨﺎﺧﺘﻪ ﻣﻲﺷﻮد .اﻳﻦ ﻣﻴﺰان ﺑـﺮاي داروﻫـﺎي آﻣﻔﻮﺗﺮﻳـﺴﻴﻦ Bو
ﺳﺎﻳﺮ ﻣﺨﻤﺮﻫﺎ
1
0/5
ﻧﻴﺴﺘﺎﺗﻴﻦ و ﻛﺎﺳﭙﻮﻓﺎﻧﮋﻳﻦ 1/0µg/ml≤MICاﺳﺖ و MIC>1/0µg/mlﺑـﻪ
ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
19
9/0
ﻣﺠﻤﻮع
205
100
ﺗﻠﻘﻴﺢ ﺷﺪه ﺑﻪﻣـﺪت 24ﺳـﺎﻋﺖ در دﻣـﺎي 35 ºCاﻧﻜﻮﺑـﻪ ﮔﺮدﻳﺪﻧـﺪ و ﺳﭙﺲ در ﻳﻚ ﻣﺤﻴﻂ SDAﺟﻬـﺖ ﺷـﻤﺎرش ﺗﻌـﺪاد ﻛﻠﻨـﻲ رﺷـﺪ ﻳﺎﻓﺘـﻪ
داروﻫــﺎ ﺗﻮﺳــﻂ CLSIﭘﻴــﺸﻨﻬﺎد ﺷــﺪه اﺳــﺖ .ﺑــﺮاي ﻓﻠﻮﻛﻮﻧــﺎزول 8µg/ml≤MICﺑﻪ ﻋﻨﻮان ﺣﺴﺎس MIC:16-32µg/ml ،ﺑﻪ ﻋﻨﻮان ﺣﺴﺎس
18و17
ﻋﻨﻮان ﻣﻘﺎوم ﺷﻨﺎﺧﺘﻪ ﺷﺪه اﺳﺖ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻓﺮزاد ﻛﺘﻴﺮاﺋﻲ و ﻫﻤﻜﺎران
99
ﺟﺪول :2 -ﺣﺴﺎﺳﻴﺖ ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷﺪه از ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ HIVﺑﺮ اﺳﺎس ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث و اﻧﺘﺸﺎر دﻳﺴﻚ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ آﻣﻔﻮﺗﺮﻳﺴﻴﻦ
B
ﻧﻴﺴﺘﺎﺗﻴﻦ
ﻓﻠﻮﻛﻮﻧﺎزول
ﻛﺘﻮﻛﻮﻧﺎزول
ﻛﻠﻮﺗﺮﻳﻤﺎزول
ﻛﺎﺳﭙﻮﻓﺎﻧﮋﻳﻦ
ﮔﻮﻧﻪﻫﺎي ﻣﺨﻤﺮي
اﻧﺘﺸﺎر دﻳﺴﻚ
ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ﺑﺮاث MIC Rang
MIC90 µg/ml
ﺣﺴﺎس %
0/03-4
0/125
96/2
واﺑﺴﺘﻪ ﺑﻪ دوز % 1
2/9
0/03-0/5
0/125
95/6
4/4
0
0/06-0/5
0/125
100
0
0
0/03-1
0/125
92/3
7/7
0
ﻣﻘﺎوم %
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
0/125-0/25
0/125
100
0
0
0/06-0/125
0/125
100
0
0
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
0/06-1
0/125
85
11/7
3/3
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
0/06-1
0/125
98/1
1/9
0
0/06-0/25
0/125
100
0
0
0/06-0/25
0/125
100
0
0
0/06-0/25
0/125
100
0
0
0/06-0/125
0/125
100
0
0
0/03-0/25
0/125
100
0
0
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
0/03-0/25
0/125
100
0
0
1-128
8
55/2
19/1
25/7
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
2-128
128
37/9
4/4
57/7
1-128
4
77/8
11/1
11/1
2-128
8
56/2
17/7
26/2
1-128
16
60
16/7
23/3
2-128
4
67/1
0
32/9
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
1-128
16
64
25/2
10/8
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
0/06-8
0/125
63/3
14/8
21/9
0/06-8
0/125
55/6
13/3
31/1
0/06-0/125
0/06
100
0
0
0/06-8
0/125
56/2
23/1
20/8
0/06-0/5
0/06
76/7
23/3
0
0/06-4
0/125
67/1
0
32/9
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
0/06-4
0/06
79/6
10/2
10/2
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
0/06-8
0/125
75/7
11/9
16/4
0/03-8
0/25
60
4/4
35/6
0/125-0/25
0/06
100
0
0
0/06-4
0/06
79/2
15/4
5/4
0/125-1
0/125
60
28/3
11/7
0/06-8
0/125
67/1
0
32/9
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
0/125-0/25
0/125
100
0
0
ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘﺴﻴﻠﻮزﻳﺲ ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ
0/06-1
0/125
100
0
0
0/06-0/25
0/125
100
0
0
0/06-0/25
0/125
100
0
0
0/06-0/25
0/125
100
0
0
0/06-0/125
0/125
100
0
0
0/03-0/25
0/125
100
0
0
ﺳﺎﻳﺮ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
0/03-0/25
0/125
100
0
0
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺑﺮرﺳﻲ ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪاﺷﺪه از اﻓﺮاد HIVﻣﺜﺒﺖ ﻣﺒﺘﻼ ﺑﻪ ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ
100
ﻣﻘﺪار MIC-%90داروي ﻓﻠﻮﻛﻮﻧﺎزول ﺑﺮاي ﻛﺎﻧﺪﻳـﺪا آﻟﺒﻴﻜـﻨﺲ 8µg/ml
اﻓﺰاﻳﺶ ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻧﻘﺎﻳﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ از ﻣﻬﻢﺗـﺮﻳﻦ ﻋﻮاﻣـﻞ ﻳـﺎ
ﺑــﻪدﺳــﺖ آﻣــﺪه اﺳــﺖ .اﻳــﻦ ﻣﻘــﺪار ﺑــﺮاي داروي ﻛﺘﻮﻛﻮﻧــﺎزول و
ﻓﺎﻛﺘﻮرﻫﺎي دﺧﻴﻞ در اﭘﻴﺪﻣﻴﻮﻟﻮژي ﺑﻴﻤـﺎري ﻛﺎﻧﺪﻳـﺪﻳﺎزﻳﺲ و ﺧـﺼﻮﺻﺎ
ﻛﻠﻮﺗﺮﻳﻤﺎزول ﺑﺮاﺑـﺮ ﺑـﺎ 0/125µg/mlﻣـﻲﺑﺎﺷـﺪ .در راﺑﻄـﻪ ﺑـﺎ ﺟﺪاﻳـﻪ
ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ اﺳﺖ .ﺗﻌﻴﻴﻦ اﻟﮕﻮي ﺣﺴﺎﺳﻴﺖ ﺑﻪ داروﻫـﺎي ﺿـﺪ
(ATCCﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﺑﻪﻋﻨﻮان ﻳﻚ ﻧﻤﻮﻧـﻪ ﻣﻘـﺎوم
ﻗﺎرﭼﻲ و ﺷﻨﺎﺳﺎﻳﻲ ﻳـﺎ ﺗـﺸﺨﻴﺺ ﻇﻬـﻮر ﻣﻘﺎوﻣـﺖ از اﻫﻤﻴـﺖ وﻳـﮋهاي
واﺑﺴﺘﻪ ﺑﻪ دوز داروي آزول ﻧﺘﺎﻳﺞ ﺑﻪدﺳﺖ آﻣﺪه ﺑﺎ واﺑﺴﺘﻪ ﺑﻪ دوز ﺑـﻮدن
ﺑﺮﺧﻮردار اﺳﺖ زﻳﺮا ﻣﻘﺎوﻣﺖ ﺑﻪ داروﻫﺎ ﻣﻬﻢﺗـﺮﻳﻦ ﻣﻌـﻀﻞ ﺑـﺮ ﺳـﺮ راه
Candida dubliniensis
درﻣﺎن اﻳﻦ ﺑﻴﻤﺎريﻫﺎ اﺳﺖ .در ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ دو روش اﻧﺘـﺸﺎر دﻳـﺴﻚ
) (CD36ﺑﻪ ﻋﻨﻮان ﺟﺪاﻳﻪ ﺣﺴﺎس ﺑﻪ داروي آزول ﻧﺘﺎﻳﺞ ﺑﻪدﺳﺖ آﻣﺪه ﺑﺎ
و ﻣﻴﻜﺮوﺑﺮاث داﻳﻠﻮﺷﻦ ﺑﺮاي 200ﮔﻮﻧﻪ ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷﺪه از ﺑﻴﻤـﺎران
ﺣﺴﺎس ﺑﻮدن آن ﻣﻄـﺎﺑﻖ ﺑـﻮد .ﻣﻴـﺰان ﻣﻘﺎوﻣـﺖ ﻛﺎﻧﺪﻳـﺪا آﻟﺒﻴﻜـﻨﺲ ﺑـﻪ
آﻟﻮده ﺑﻪ HIVﺑﻪﻛﺎر ﺑﺮده ﺷﺪ ﻛﻪ 98ﮔﻮﻧﻪ آن ﮔﻮﻧﻪﻫـﺎي ﻏﻴـﺮ آﻟﺒﻴﻜـﻨﺲ
داروﻫﺎي ﮔﺮوه ﭘﻠﻲ ان ﺷﺎﻣﻞ آﻣﻔﻮﺗﺮﻳﺴﻴﻦ و ﻧﻴـﺴﺘﺎﺗﻴﻦ در ﺣـﺪ ﭘـﺎﻳﻴﻨﻲ
ﺑﻮدهاﻧﺪ و اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺟﺪﻳﺪﺗﺮﻳﻦ ﺑﺮرﺳﻲ اﻧﺠﺎم ﺷﺪه در راﺳﺘﺎي ﺗﻌﻴـﻴﻦ
ﺑﻪدﺳﺖ آﻣﺪ )ﺑﻪ ﺗﺮﺗﻴﺐ 2/9و ﺻﻔﺮ درﺻﺪ( .ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ -دوﻣـﻴﻦ
ﺣﺴﺎﺳﻴﺖ داروﻳﻲ ﺑﺮ روي اﻳﻦ ﺑﻴﻤﺎران در اﻳﺮان اﺳﺖ .ﻧﺘﺎﻳﺞ ﺑـﻪدﺳـﺖ
ﮔﻮﻧﻪ ﺟﺪا ﺷﺪه از ﻧﻈﺮ ﺷﻴﻮع در اﻳﻦ ﻣﻄﺎﻟﻌﻪ -ﻣﻘﺎوﻣﺖ ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ ﺑـﻪ
آﻣﺪه در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن ﻣﻲدﻫـﺪ اﻧـﻮاع ﻣﺨﺘﻠﻔـﻲ از ﮔﻮﻧـﻪﻫـﺎي ﻏﻴـﺮ
داروي ﻓﻠﻮﻛﻮﻧﺎزول ﻧﺸﺎن داد ﺑﻪﻃﻮري ﻛﻪ %57/7از ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا
آﻟﺒﻴﻜﻨﺲ ﺷﺎﻣﻞ ﻛﺎﻧﺪﻳﺪا ﺗﺮوﭘﻴﻜﺎﻟﻴﺲ ،ﻛﺎﻧﺪﻳﺪا ﭘﺎراﭘـﺴﻴﻠﻮزﻳﺲ ،ﻛﺎﻧﺪﻳـﺪا
ﮔﻼﺑﺮاﺗﺎ داراي MIC>125µg/mlﺑﺮاي اﻳﻦ دارو ﺑﻮدهاﻧﺪ .ﻫﻢﭼﻨﻴﻦ ﻣﻴﺰان
ﮔﻴﻠﺮﻣﻮﻧﺪي و ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ از اﻳﻦ ﺑﻴﻤﺎران ﺟﺪا ﻣﻲﺷﻮد .در ﺑﻴﻦ اﻳـﻦ
ﻣﻘﺎوﻣﺖ ﺑﻪ داروﻫﺎي ﻛﺘﻮﻛﻮﻧﺎزول و ﻛﻠﻮﺗﺮﻳﻤﺎزول ﺑـﻪ ﺗﺮﺗﻴـﺐ 31و 35
ﮔﻮﻧﻪﻫﺎي ﻏﻴـﺮ آﻟﺒﻴﻜـﻨﺲ ﻛﺎﻧﺪﻳـﺪا داﺑﻠـﻲ ﻧﻴﻨـﺴﻴﺲ ﺑـﺎ اﻳﺠـﺎد ﺑﻴﻤـﺎري
.(MICدر راﺑﻄﻪ ﺑﺎ ﻛﺎﻧﺪﻳـﺪا
20
داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ ﺑﺎﻻﻳﻲ ﻧﺴﺒﺖ ﺑﻪ داروﻫـﺎي ﮔـﺮوه آزول
ﻣﻄﺎﺑﻖ ﺑﺎ ﺑﺴﻴﺎري از ﻣﻄﺎﻟﻌﺎت ﺻﻮرت ﮔﺮﻓﺘـﻪ در ﺳﺮاﺳـﺮ دﻧﻴـﺎ ﻛﺎﻧﺪﻳـﺪا
ﺑﻪدﺳﺖ آﻣﺪ ﺑـﻪﻃـﻮريﻛـﻪ %77/8ﺟﺪاﻳـﻪﻫـﺎ ﻧـﺴﺒﺖ ﺑـﻪ ﻓﻠﻮﻛﻮﻧـﺎزول
آﻟﺒﻴﻜﻨﺲ ﺷﺎﻳﻊﺗﺮﻳﻦ ﮔﻮﻧﻪ ﻛﺎﻧﺪﻳﺪا در اﻳﺠﺎد ﺑﻴﻤﺎري و ﺷﺎﻳﻊﺗـﺮﻳﻦ ﮔﻮﻧـﻪ
ﺣﺴﺎﺳﻴﺖ ﻧﺸﺎن دادﻧﺪ و %11/1ﻧﻴﺰ ﺣﺴﺎﺳﻴﺖ واﺑﺴﺘﻪ ﺑـﻪ دوز داﺷـﺘﻨﺪ.
ﺟﺪا ﺷﺪه از ﺑﻴﻤـﺎران HIVاﺳـﺖ ،ﻫﺮﭼﻨـﺪ ﻣﻴـﺰان ﺟﺪاﺳـﺎزي ﻛﺎﻧﺪﻳـﺪا
ﻫﻢﭼﻨﻴﻦ %100از ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا داﺑﻠﻲ ﻧﻴﻨﺴﻴﺲ ﺑﻪ ﻛﺘﻮﻛﻮﻧـﺎزول و
ﮔﻼﺑﺮاﺗﺎ ﻗﺎﺑﻞ ﺗﻮﺟﻪ و دور از اﻧﺘﻈﺎر ﺑـﻮده اﺳـﺖ .ﺑـﺮ اﺳـﺎس ﻣﻄﺎﻟﻌـﺎت
ﻛﻠﻮﺗﺮﻳﻤﺎزول ﺣﺴﺎﺳﻴﺖ ﻧﺸﺎن دادﻧﺪ .ﻛﺎﻧﺪﻳﺪا ﻛﻔﻴﺮ ﺑﻪﻋﻨﻮان ﻳـﻚ ﮔﻮﻧـﻪ
ﺻﻮرت ﮔﺮﻓﺘﻪ در ﺳﺎﻳﺮ ﻛﺸﻮرﻫﺎ ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﺑـﻪ ﻋﻨـﻮان اوﻟـﻴﻦ ﻳـﺎ
ﺣﺴﺎس ﺑﻪ داروﻫﺎي آزول ﺷﻨﺎﺧﺘﻪ ﺷﺪه اﺳﺖ ،در ﺻﻮرﺗﻲﻛﻪ %32/9از
دوﻣﻴﻦ ﮔﻮﻧﻪ ﺷﺎﻳﻊ ﻏﻴﺮ آﻟﺒﻴﻜﻨﺲ در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ HIVﮔﺰارش ﺷـﺪه
ﺟﺪاﻳﻪﻫﺎي ﺑﻪدﺳﺖ آﻣﺪه در اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﺑـﻪ داروﻫـﺎي آزول ﻣﻘﺎوﻣـﺖ
اﺳﺖ 21-23.ذﻛﺮ اﻳﻦ ﻧﻜﺘﻪ ﺿﺮوري ﺑﻪﻧﻈﺮ ﻣﻲرﺳﺪ ﻛـﻪ ﻛﻠﻮﻧﻴﺰاﺳـﻴﻮن ﺑـﺎ
اﺳﺘﺎﻧﺪارد
)10231
آن ﻣﻄﺎﺑﻘﺖ داﺷﺖ ،ﻫﻢﭼﻨﻴﻦ ﺟﺪاﻳﻪ اﺳـﺘﺎﻧﺪارد
درﺻﺪ ﺑﻪدﺳﺖ آﻣﺪ
)range:0/06-8µg/ml
ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ -ﺣﻠﻘﻲ در ﺑﻴﻤﺎران HIVﻣﺜﺒﺖ در ارﺗﺒﺎط اﺳـﺖ.
24
ﻧﺸﺎن دادﻧﺪ و ﺗﻤﺎم اﻳﻦ ﺟﺪاﻳﻪﻫﺎي ﻣﻘﺎوم از ﺑﻴﻤﺎران ﻣﺒـﺘﻼ ﺑـﻪ ﺑﻴﻤـﺎري
ﻛﺎﻧﺪﻳﺪا ﮔﻼﺑﺮاﺗﺎ ﭘﺲ از درﻣﺎن ﺑﺎ ﻓﻠﻮﻛﻮﻧـﺎزول اﻓـﺰاﻳﺶ ﻣـﻲﻳﺎﺑـﺪ .در
ﻋﻮد ﻛﻨﻨﺪه ﻛﺎﻧﺪﻳﺪاﻳﻲ ﺑﻪدﺳﺖ آﻣﺪه اﺳﺖ .در ﻣﺠﻤﻮع ﻣﻴﺰان ﻣﻘﺎوﻣﺖ ﺑﻪ
راﺑﻄﻪ ﺑﺎ آزﻣﺎﻳﺸﺎت ﺗﻌﻴﻴﻦ ﺣﺴﺎﺳﻴﺖ ﺑـﻪ داروﻫـﺎي ﺿـﺪ ﻗـﺎرﭼﻲ از دو
داروﻫﺎي آزول ﻓﺮاﮔﻴﺮ اﺳﺖ .ﺗﻔﺎوت ﻗﺎﺑـﻞ ﺗـﻮﺟﻬﻲ ﺑـﻴﻦ ﺑﻴﻤـﺎراﻧﻲ ﻛـﻪ
روش ﻣﻮرد ﺗﺎﻳﻴﺪ CLSIاﺳﺘﻔﺎده ﺷﺪه اﺳﺖ ﻛﻪ اﻟﺒﺘﻪ در راﺑﻄﻪ ﺑﺎ ﻣﺰاﻳـﺎ و
داروﻫﺎي آزول درﻳﺎﻓﺖ ﻛﺮدﻧﺪ و آندﺳﺘﻪ ﻛﻪ اﻳﻦ داروﻫـﺎي را درﻳﺎﻓـﺖ
ﻣﻌﺎﻳﺐ و ﻧﻜﺎت ﺗﻜﻨﻴﻜﻲ اﻳﻦ روشﻫﺎ ﺑﺤﺚ ﺑـﺴﻴﺎر اﺳـﺖ و ﻣﺠـﺎل آن
ﻧﻤﻲﻛﺮدﻧﺪ در ﺟﺪاﺳﺎزي ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﻣﻘﺎوم ﺑـﻪ آزول ﻣـﺸﺎﻫﺪه
ﻧﻴﺴﺖ .ﺑـﻪﻃـﻮر ﻣﻌﻤـﻮل ﻣﻘﺎوﻣـﺖ ﺑـﻪ داروي آﻣﻔﻮﺗﺮﻳـﺴﻴﻦ Bدر ﺑـﻴﻦ 25
ﮔﺮدﻳﺪ ) .(P:0/02ﻛﻠﻴﻪ ﺟﺪاﻳﻪﻫﺎي ﺑﻪدﺳﺖ آﻣﺪه ﮔﻮﻧـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪاﻳﻲ
ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا درﺻﺪ ﻛﻤﻲ را ﺷﺎﻣﻞ ﻣﻲﺷﻮد و در ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ
در اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﺑـﻪ داروي ﻧﻴـﺴﺘﺎﺗﻴﻦ ،آﻣﻔﻮﺗﺮﻳـﺴﻴﻦ Bو ﻛﺎﺳـﭙﻮﻓﺎﻧﮋﻳﻦ
ﺣﺴﺎﺳﻴﺖ ﺑﻪ داروي آﻣﻔﻮﺗﺮﻳﺴﻴﻦ Bو ﻧﻴﺴﺘﺎﺗﻴﻦ ﻛﻪ از داروﻫﺎي ﺧﺎﻧﻮاده
ﺣﺴﺎﺳﻴﺖ ﻧﺸﺎن دادﻧﺪ.
ﭘﻠﻲ انﻫﺎ داروي ﻛﺎﺳﭙﻮﻓﺎﻧﮋﻳﻦ از ﺧﺎﻧﻮاده اﻛﻴﻨﻮﻛﺎﻧـﺪﻳﻦﻫـﺎ ﻗﺎﺑـﻞ ﺗﻮﺟـﻪ ﺑﻮد ،ﻫﺮ ﭼﻨﺪ در ﻣﻮارد اﻧﺪﻛﻲ ﻧﻴﺰ ﻧﺴﺒﺖ ﺑﻪ داروي آﻣﻔﻮﺗﺮﻳﺴﻴﻦ در ﺑﻴﻦ
ﺑﺤﺚ
ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ﻣﻘﺎوﻣﺖ ﻣﺸﺎﻫﺪه ﮔﺮدﻳﺪ )ﻛـﻢﺗـﺮ از .(%3اﻳـﻦ ﻳﺎﻓﺘـﻪ ﻣﻄﺎﺑﻖ ﺑﺎ ﺳﺎﻳﺮ ﻣﻄﺎﻟﻌﺎت اﻧﺠﺎم ﮔﺮﻓﺘﻪ اﺳﺖ ﻧﺸﺎن ﻣﻲدﻫﺪ ﻣﻴﺰان ﻣﻘﺎوﻣﺖ
ﻇﻬـﻮر ﮔﻮﻧـﻪﻫـﺎي ﻛﺎﻧـﺪﻳـﺪاي ﻣﻘـﺎوم ﺑـﻪ داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ و
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺑﻪ اﻳﻦ دارو ﭘﺎﻳﻴﻦ اﺳﺖ ،ﻫﺮ ﭼﻨﺪ Badieeدر ﺑﻴﻤﺎران ﻧﻘﺺ اﻳﻤﻨﻲ ﻣﻴﺰان
F.و ﻫﻤﻜﺎران ﻓﺮزادal.ﻛﺘﻴetﺮاﺋﻲ Katiraee
ﻣﻘﺎوﻣﺖ ﺑﻪ دارو را در ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ در ﺣﺪود %7ﮔﺰارش ﻧﻤﻮده و
101
ﺑﻪﻧﺤﻮي ﺑﺎﻳﺪ ﺷﺮاﻳﻂ واردات ﻳﺎ ﺗﻮﻟﻴﺪ داروﻫﺎي ﺟﺪﻳﺪ را ﻣﻬﻴﺎ ﻛﻨﻨـﺪ .در
26-28و22
ﻣﻘﺎﻳﺴﻪ ﺑﺎ روش ﻣﻴﻜﺮوداﻳﻠﻮﺷﻦ ،در روش اﻧﺘﺸﺎر دﻳﺴﻚ ﻧﻴﺰ ﻧﺘﺎﻳﺞ ﻗﺎﺑﻞ
در ﺑﺮﺧﻲ ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮ اﻳﻦ ﻣﻴﺰان ﺗﺎ ﺣـﺪود %8ﺑـﻮده اﺳـﺖ.
ﻋﻠﻲرﻏﻢ ﺳﺎﻳﺮ ﻣﻄﺎﻟﻌﺎت اﻧﺠﺎم ﺷﺪه ،ﺑﺎ وﺟﻮد آنﻛـﻪ در ﺑﻴﻤـﺎران ﻣـﻮرد
ﻗﺒﻮﻟﻲ ﺑﻪدﺳﺖ آﻣﺪ و اﺧﺘﻼف ﻣﻌﻨﻲداري ﺑﻴﻦ اﻳﻦ دو روش دﻳﺪه ﻧـﺸﺪ.
ﺑﺮرﺳﻲ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺗﺠـﻮﻳﺰ ﻧﻴـﺴﺘﺎﺗﻴﻦ راﻳـﺞ ﺑـﻮده اﺳـﺖ اﻣـﺎ ﻫـﻴﭻ
ﺑﻪﻧﻈﺮ ﻣﻲرﺳﺪ اﺳﺘﻔﺎده از روشﻫﺎي ﺗﻌﻴﻴﻦ ﺣﺴﺎﺳﻴﺖ ﺑﻪ داروﻫﺎي ﺿـﺪ
ﻣﻘﺎوﻣﺘﻲ ﺑﻪ اﻳﻦ دارو دﻳﺪه ﻧﺸﺪ و ﻧﺸﺎن ﻣﻲدﻫﺪ اﻳﻦ دارو ﻫـﻢﭼﻨـﺎن ﺑـﻪ
ﻗــﺎرﭼﻲ ﻧﻴــﺰ ﺑــﻪراﺣﺘــﻲ ﺑــﺎ اﺳــﺘﻔﺎده از روش اﻧﺘــﺸﺎر دﻳــﺴﻚ در
ﻋﻨﻮان ﻳﻚ داروي ﻣﻮﺛﺮ ﺑﺮاي ﭘﻴﺸﮕﻴﺮي از ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ﻣﻨﺎﺳﺐ
آزﻣﺎﻳﺸﮕﺎهﻫﺎي روﺗﻴﻦ ﻗﺎﺑﻞ اﻧﺠﺎم ﺑﺎﺷﺪ و ﺑﻪﻧﺤﻮي ﺑﺎﻳﺪ در دﺳـﺘﻮر ﻛـﺎر
اﺳﺖ .ﻫﺮﭼﻨﺪ ﻛﻪ ﻣﺼﺮف ﻣﻮﺿﻌﻲ و ﻓﻘﺪان ﺟﺬب ﺳﻴﺴﺘﻤﻴﻚ در ﻣـﻮرد
ﻗﺮار ﮔﻴﺮد .ﺑـﻪﻃـﻮر ﺧﻼﺻـﻪ ،در اﻳـﻦ ﺗﺤﻘﻴـﻖ اﻟﮕـﻮي ﺣـﺴﺎﺳﻴﺖ ﺑـﻪ
اﻳــﻦ دارو از دﻻﻳــﻞ ﻋــﺪم ﻛــﺎرﺑﺮد آن ﺑــﺮاي ﺑﻴﻤــﺎري ﺳﻴــﺴﺘﻤﻴﻚ و
داروﻫﺎي ﺿﺪ ﻗﺎرﭼﻲ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ﺑﻪدﺳﺖ آﻣﺪه از ﺑﻴﻤﺎران آﻟـﻮده
ﻛﺎﻧﺪﻳـﺪﻳﺎزﻳﺲ ﻣــﺮي اﺳــﺖ .ﻣﻘﺎوﻣــﺖ ﺑــﻪ داروي ﻓﻠﻮﻛﻮﻧــﺎزول در اﺛــﺮ
ﺑﻪ HIVﻣﺮاﺟﻌﻪ ﻛﻨﻨﺪه ﺑﻪ ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت اﻳﺪز اﻳﺮان واﻗﻊ در ﺑﻴﻤﺎرﺳـﺘﺎن
اﺳﺘﻔﺎده ﻃﻮﻻﻧﻲ ﻣﺪت از اﻳﻦ دارو ﺗﻮﺳﻂ ﺳﺎﻳﺮ ﻣﺤﻘﻘﻴﻦ ﺑﻪ اﺛﺒﺎت رﺳﻴﺪه
اﻣﺎمﺧﻤﻴﻨﻲ ﺗﻬﺮان ﺑﺮرﺳـﻲ ﺷـﺪ .درﺻـﺪ ﺑـﺎﻻي ﺟﺪاﺳـﺎزي ﮔﻮﻧـﻪﻫـﺎي
اﺳﺖ 29.ﺑﻨﺎﺑﺮاﻳﻦ اﻳـﻦﻛـﻪ ﻓﻠﻮﻛﻮﻧـﺎزول داروي ﻛـﺎﻣﻼ ﻣـﻮﺛﺮي در ﺑﺮاﺑـﺮ
ﻛﺎﻧﺪﻳﺪاي ﻏﻴﺮ آﻟﺒﻴﻜﻨﺲ زﻧﮓ ﺧﻄﺮ ﺗﻐﻴﻴﺮ در اﭘﻴﺪﻣﻴﻮﻟﻮژي ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ
ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا و ﺑﻪﻃﻮر ﺧﺎص ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ )ﺑﻪﻋﻨﻮان ﺷﺎﻳﻊﺗﺮﻳﻦ
دﻫﺎﻧﻲ را در ﺑﻴﻤﺎران اﻳﺮاﻧﻲ در آورده اﺳﺖ .ﺑﺮ اﺳﺎس ﻧﺘـﺎﻳﺞ ﺑـﻪدﺳـﺖ
ﮔﻮﻧﻪ در اﻳﺠﺎد ﺑﻴﻤﺎريﻫـﺎي ﻛﺎﻧﺪﻳـﺪاﻳﻲ( ﻧﺒﺎﺷـﺪ دور از ذﻫـﻦ ﻧﻴـﺴﺖ،
آﻣﺪه ،ﻧﻮﻳﺴﻨﺪﮔﺎن اﻳﻦ ﻣﻘﺎﻟﻪ ﺑﺮرﺳـﻲ و ردﻳـﺎﺑﻲ ﺟﺪاﻳـﻪﻫـﺎي ﻛﺎﻧﺪﻳـﺪاي
ﺑﻪﻃﻮريﻛﻪ در ﺣﺪود %25از ﺟﺪاﻳﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا آﻟﺒﻴﻜﻨﺲ ﻣﻘﺎوﻣﺖ ﺑـﻪ
ﻣﻘــﺎوم ﺑــﻪ دارو را ﺑــﺎ روش اﻧﺘــﺸﺎر دﻳــﺴﻚ و رﻗــﺖﺳــﺎزي ﻣــﺎﻳﻊ در
ﻓﻠﻮﻛﻮﻧﺎزول را ﻧﺸﺎن دادﻧﺪ .ﻳﺎﻓﺘﻪ اﺧﻴﺮ ﺗﺎ ﺣﺪودي از ﻧﻈﺮ درﺟﻪ و ﻣﻴﺰان
آزﻣﺎﻳﺸﮕﺎهﻫﺎي ﺑﺎﻟﻴﻨﻲ ﺑﺮاي اراﻳﻪ ﺧﺪﻣﺎت ﺑﻬﺘﺮ ﺑﻪ ﺑﻴﻤﺎران ﻣﺒـﺘﻼ ﺗﻮﺻـﻴﻪ
ﻣﻘﺎوﻣﺖ ﺑﻪ اﻳﻦ دارو ﺑﺎ ﺳـﺎﻳﺮ ﮔﺰارﺷـﺎت اراﻳـﻪ ﺷـﺪه ﻣﺘﻔـﺎوت اﺳـﺖ.
ﻣﻲﻛﻨﻨﺪ .ﺑﺎ وﺟﻮد آنﻛﻪ ﻧﻴﺴﺘﺎﺗﻴﻦ ﺑﻪﻃﻮر ﮔﺴﺘﺮده در اﻳﻦ ﺑﻴﻤـﺎران ﻣـﻮرد
ﻫﺮﭼﻨﺪ در ﺑﺴﻴﺎري از ﻣﻄﺎﻟﻌﺎت ﻣﻘﺎوﻣـﺖ ﺑـﻪ اﻳـﻦ دارو ﮔـﺰارش ﺷـﺪه
ﻣﺼﺮف ﺑﻮده اﺳﺖ و ﻣﻘﺎوﻣﺘﻲ در ﺑﺮاﺑﺮ اﻳﻦ دارو دﻳﺪه ﻧﺸﺪ ﺗﺠﻮﻳﺰ اﻳـﻦ
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دارو ﺑﺮاي ﭘﻴﺸﮕﻴﺮي از ﺑﻴﻤﺎري ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ ﺗﻮﺻﻴﻪ ﻣﻲﺷﻮد .از
اﺣﺘﻤﺎل ﻣﻲرود ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ اﻳﻦﻛﻪ ﺟﻤﻌﻴﺖ ﻣﻮرد ﺑﺮرﺳﻲ ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ
ﻃﺮﻓﻲ ﻣﻴﺰان ﺑﺎﻻي ﻣﻘﺎوﻣﺖ ﺑﻪ داروﻫﺎي آزول ،ﺧﺼﻮﺻﺎ ﻓﻠﻮﻛﻮﻧﺎزول ﻣﺎ
ﺑﻪ وﻳﺮوس ﻧﻘﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ ﺑﻮده اﺳﺖ و اﻳﻦ ﺑﻴﻤـﺎران در ﺑـﻴﺶﺗـﺮ
را در اﺳﺘﻔﺎده از اﻳﻦ دارو ﺑﻪ ﻋﻨﻮان داروي ﭘﻴﺸﮕﻴﺮي ﻛﻨﻨـﺪه از ﺑﻴﻤـﺎري
ﻣﻮارد ﺳﺎﺑﻘﻪ درﻣﺎنﻫﺎي ﻗﺒﻠﻲ و ﻣﺪاوم را داﺷﺘﻪاﻧـﺪ ،ﻣﻴـﺰان ﻣﻘﺎوﻣـﺖ در
دﻫﺎﻧﻲ ﻛﺎﻧﺪﻳﺪا ﺑﺎ ﺗﺮدﻳﺪ ﻣﻮاﺟﻪ ﻣﻲﻛﻨﺪ.
اﺳﺖ اﻣﺎ درﺻﺪ ﻣﻘﺎوﻣﺖ ﻧﺴﺒﺖ ﺑﻪ اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻛﻢﺗـﺮ ﺑـﻮده اﺳـﺖ.
ﺳﭙﺎﺳﮕﺰاري :اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﺑﺨﺸﻲ از ﭘﺎﻳـﺎنﻧﺎﻣـﻪ ﺗﺤـﺖ ﻋﻨـﻮان
آنﻫﺎ ﺑﻴﺶﺗﺮ ﺑﻮده اﺳﺖ .ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ آزﻣﺎﻳـﺸﺎت اﻧﺠـﺎم ﺷـﺪه در اﻳـﻦ
"ﺗﻌﻴﻴﻦ ژﻧﻮﺗﺎﻳﭗ و اﻟﮕﻮي ﺣﺴﺎﺳﻴﺖ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪاي ﺟﺪا ﺷـﺪه از
ﻣﻄﺎﻟﻌﻪ ﻣﻴﺰان ﺣﺴﺎﺳﻴﺖ در ﺑﻴﻦ ﮔﻮﻧﻪﻫﺎي ﻛﺎﻧﺪﻳﺪا ﺑﻪﺗﺮﺗﻴﺐ زﻳﺮ اﺳﺖ:
ﺑﻴﻤﺎران آﻟﻮده ﺑﻪ وﻳﺮوس HIVﻣﺒﺘﻼ ﺑﻪ ﻛﺎﻧﺪﻳﺪﻳﺎزﻳﺲ دﻫﺎﻧﻲ در اﻳﺮان"،
> C. dubliniensis> C. kefyr > C. parapsilosis > C. tropicalis C. albicans > C. Krusei > C.glabrata.
در ﻣﻘﻄﻊ دﻛﺘﺮاي ﺗﺨﺼﺼﻲ در ﺳﺎل 1388ﺑﻪ ﻛﺪ 380ﻣﻲﺑﺎﺷﺪ ﻛـﻪ ﺑـﺎ
ﻣﺘﺎﺳﻔﺎﻧﻪ ﺑﻪدﻟﻴﻞ در دﺳﺘﺮس ﻧﺒﻮدن داروي ﺟﺪﻳﺪ ﺿﺪ ﻗـﺎرﭼﻲ و ﻳـﺎ در
ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه ﺗﻬﺮان اﻧﺠﺎم ﺷـﺪه اﺳـﺖ .ﻧﻮﻳـﺴﻨﺪﮔﺎن ﻣﻘﺎﻟـﻪ از ﻛﻠﻴـﻪ
ﭘﺎرهاي ﻣﻮارد ﮔﺮاﻧﻲ ﺑﺮﺧﻲ داروﻫﺎ ﺑﻴﻤﺎران راﻫـﻲ ﺟـﺰ ﻣـﺼﺮف داروي
ﻫﻤﻜﺎراﻧﻲ ﻛﻪ در اﻳـﻦ ﺗﺤﻘﻴـﻖ ﻣـﺎ را ﻳـﺎري ﻧﻤﻮدﻧـﺪ ،ﺗﻘـﺪﻳﺮ و ﺗـﺸﻜﺮ
ﻓﻠﻮﻛﻮﻧﺎزول را ﻧﺪارﻧﺪ .ﺑﻪﻧﻈﺮ ﻣﻲرﺳـﺪ ﭘﺰﺷـﻜﺎن ﻣـﻲﺑﺎﻳـﺴﺖ ﺗﻮﺟـﻪ و
ﻣﻲﻧﻤﺎﻳﻨﺪ و ﺑﺮ ﺳـﻔﻴﺪ ﺟﺎﻣﮕـﺎن ﻋﻠـﻮم آزﻣﺎﻳـﺸﮕﺎﻫﻲ و ﭘﺮﺳـﺘﺎري درود
ﺗﻤﺎﻳﻞ ﺑﻪ ﺗﺠﻮﻳﺰ داروﻫﺎي ﺟﺪﻳـﺪ داﺷـﺘﻪ ﺑﺎﺷـﻨﺪ و ارﮔـﺎنﻫـﺎي ذﻳـﺮﺑﻂ
ﻣﻲﻓﺮﺳﺘﻨﺪ.
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In vitro antifungal susceptibility of oral candida species from Iranian HIV infected patients
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ﺟﺮاﺣﻲ ﻋﻤﻮﻣﻲMedical در ﺑﺨﺸﻬﺎي ﻣﺤﻞ ﺟﺮاﺣﻲ ﻋﻔﻮﻧﺖ روش96-103 ﻛﺎراﻳﻲ دو Tehran University Journal; Vol. 70,ﺗﺸﺨﻴﺺ No. 2, ﺑﺮاي Mayﭘﺎﻳﺶ 2012:
In vitro antifungal susceptibility of oral candida species from Iranian HIV infected patients
Abstract Farzad Katiraee Ph.D.1* Ali Reza Khosravi Ph.D.2 Vahid Khalaj Ph.D.3 Mahbobeh Hajiabdolbaghi M.D.4 Ali Asghar Khaksar D.V.M.3 Mehrnaz Rasoulinejad M.D.4 1- Mycology Research Center, Faculty of Veterinary Medicine, Azad University, Science and Research Branch, Tehran, Iran. 2- Department of Microbiology, Faculty of Veterinary Medicine, University of Tehran, Iran. 3- Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. 4- IRCHA, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Received: December 08, 2011 Accepted: January 21, 2012
Background: Oropharyngeal candidiasis and antifungal drug resistance are major problems in HIV positive patients. The increased reports of antifungal resistance and expanding therapeutic options prompted the determination of antifungal susceptibility profile of Candida species isolates in Iranian patients living with HIV/AIDS (PLWHA) in the present study. Methods: One hundred fifty oral samples from Iranian HIV positive patients were obtained and cultured on CHROMagar and Sabouraud’s dextrose agar. All isolates were identified according to assimilation profile, germ tube, colony color and other conventional methods. Disk diffusion testing and Broth Microdilution of six antifungal agents were performed according to the methods described in CLSI. Results: Candida albicans (50.2%) was the most frequent isolated yeast, followed by C. glabrata (22%). Non-Candida albicans species were isolated from 71 (61%) positive cultures. 25.7% of Candida albicans isolates were resistant to fluconazole (MIC≥64 µg/ml) as were 21.9% and 16.4% to ketoconazole and clotrimazole (MIC>0.125 µg/ml), respectively. Resistance to polyene antifungals including amphotericin B and nystatin, and caspofungin were scarce. 57.7% of candida glabrata isolates were resistant to fluconazole, 31% to ketoconazole and 35% to clotrimazole. Conclusion: Screening for antifungal resistant candida isolates by disk diffusion or broth dilution methods in clinical laboratories is an ideal surveillance measure in the management of oral thrush in patients with HIV/AIDS. Although nystatin is widely used in clinical practice for HIV positive patients, there was no evidence of enhanced resistance to it. Regarding no resistance to caspofungin, its administration is suggested.
*
Corresponding author: Mycology Research Center, Islamic Azad University, Science and Research Branch, Sarv Sq., Before Shahrvand Shop, Tehran, Iran. Tel: +98- 912- 6047311 E-mail: katiraee_f@yahoo.com
Keywords: Antifungal drug resistance, azoles, candida species, HIV infections, oral candidiasis, patients.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
104 ردﻳﺒﻬﺸﺖﻚ،1391 ﺷﻤﺎره ،2 ﭼﻨﺪ، ،70 دوره ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ، -109ران اﺳﺘﺨﻮان ﺳﺎب اﺗﺮوﻛﺎﻧﺘﺮﻳ ﻗﻄﻌﻪاي ﺗﻬﺮان،ﻫﺎي ﺷﻜﺴﺘﮕﻲ biologicدر plate داﻧﺸﻜﺪهﺗﻜﻨﻴﻚ ﻣﺠﻠﻪ ﺑﺮرﺳﻲ
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ﺑﺮرﺳﻲ ﺗﻜﻨﻴﻚ ﺻﻔﺤﻪﮔﺬاري ﺑﻴﻮﻟﻮژﻳﻚ در ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ران
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/10/11 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/09 :
ﭼﻜﻴﺪه
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ﺳﻌﻴﺪرﺿﺎ ﻣﻬﺮﭘﻮر
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ﻣﺤﻤﺪرﺿﺎ ﻃﻮاﻓﻲ ،رﺿﺎ ﺳﺮﺑﻲ *2
ﻣﺤﻤﺪرﺿﺎ آﻗﺎﻣﻴﺮﺳﻠﻴﻢ
زﻣﻴﻨﻪ و ﻫﺪف :ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ﻓﻤﻮر ﺣﺪود 10-34درﺻﺪ ﻛﻞ ﺷﻜﺴﺘﮕﻲﻫـﺎي ﻣﻔﺼﻞ ﻟﮕﻦ را ﺗﺸﻜﻴﻞ ﻣﻲدﻫﻨﺪ .درﻣﺎن ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ ﺑﺮاي ﺟﺮاﺣﺎن ارﺗﻮﭘﺪ ﻫﻤﻮاره ﻳﻜﻲ
-1ﮔﺮوه ارﺗﻮﭘﺪي ،ﺑﻴﻤﺎرﺳﺘﺎن دﻛﺘﺮ ﺷﺮﻳﻌﺘﻲ
از ﭼﺎﻟﺶﺑﺮاﻧﮕﻴﺰﺗﺮﻳﻦ ﻣﻮﺿﻮﻋﺎت ﺑﻮده اﺳﺖ .ﺗﺎﻛﻨﻮن ﺗﻜﻨﻴـﻚﻫـﺎي ﻣﺘﻔـﺎوﺗﻲ در ﺷﻜـﺴﺘﮕﻲﻫـﺎي ﭼﻨـﺪ ﻗﻄﻌـﻪاي ﺳـﺎب
داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان.
ﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﻔﺎده ﺷﺪه اﺳﺖ .ﺑﻌﻀﻲ از اﻳﻦ ﺗﻜﻨﻴﻚﻫﺎي ﻣﻮرد اﺳﺘﻔﺎده در ﺟﺮاﺣﻲ ﺑـﺎ ﻋـﻮارض و ﻣـﺸﻜﻼت ﻓﺮاواﻧـﻲ
-2داﻧﺸﺠﻮي ﭘﺰﺷﻜﻲ ،ﻣﺮﻛﺰ رﺷﺪ اﺳﺘﻌﺪادﻫﺎي
ﻫﻤﺮاه ﻫﺴﺘﻨﺪ .ﻟﺬا ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻣﻄﺎﻟﻌﺎت ﻗﺒﻠﻲ و ﻧﺘﺎﻳﺞ آنﻫﺎ ﺑﺮ آن ﺷﺪﻳﻢ ﺗﺎ ﻣﻄﺎﻟﻌﻪاي را ﻃﺮاﺣﻲ ﻛﻨـﻴﻢ ﻛـﻪ در آن ﺑﺘـﻮاﻧﻴﻢ
درﺧﺸﺎن و ﻣﺮﻛﺰ ﭘﮋوﻫﺶﻫﺎي ﻋﻠﻤﻲ داﻧﺸﺠﻮﻳﺎن، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان
ﻛﺎراﻳﻲ ﻓﻴﻜﺴﺎﺳﻴﻮن ﺑﻴﻮﻟﻮژﻳﻚ در ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌـﻪاي ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ اﺳـﺘﺨﻮان ﻓﻤـﻮر را ﺑﺮرﺳـﻲ ﻛﻨـﻴﻢ. روش ﺑﺮرﺳﻲ :در اﻳﻦ ﻣﻄﺎﻟﻌﻪ 20ﺑﻴﻤﺎر ﺑﺎ ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ﻓﻤﻮر ﺑﺮرﺳﻲ ﺷـﺪﻧﺪ. ﺑﻴﻤﺎران ﺑﻪ ﺻﻮرت ﺑﺎﻟﻴﻨﻲ ﺑﺮاي درد ،ﻣﻴﺰان ﺣﺮﻛﺖ ﻣﻔﺎﺻﻞ ﻫﻴﭗ و زاﻧﻮ ،اﻧﺤﺮاﻓـﺎت ﭼﺮﺧـﺸﻲ و اﺧـﺘﻼف ﻃـﻮل دو ﭘـﺎ ﺑﺮرﺳﻲ ﺷﺪﻧﺪ ،در ﺿﻤﻦ ،ﭼﮕﻮﻧﮕﻲ ﺟﻮشﺧﻮردﮔﻲ ﺑﺮ اﺳﺎس ﻳﺎﻓﺘﻪﻫﺎي رادﻳﻮﮔﺮاﻓﻲ ﺑﺮرﺳﻲ ﺷﺪ .ﻳﺎﻓﺘﻪﻫـﺎ :از ﺑﻴـﺴﺖ و ﺳﻪ ﺑﻴﻤﺎر ﭘﺬﻳﺮﻓﺘﻪ ﺷﺪه ﺑﺎ ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌـﻪاي ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ 20 ،ﺑﻴﻤـﺎر وارد ﻣﻄﺎﻟﻌـﻪ ﺷـﺪﻧﺪ .ﺑـﺮ اﺳـﺎس ﻃﺒﻘﻪﺑﻨﺪي ،Seinheimerﭼﻬﺎر ﺑﻴﻤﺎر دﭼﺎر ﺷﻜﺴﺘﮕﻲ از ﺗﻴﭗ ﺳﻪ 9 ،ﺷﻜﺴﺘﮕﻲ از ﺗﻴـﭗ ﭼﻬـﺎر و ﻫﻔـﺖ ﻧﻔـﺮ از ﺑﻴﻤـﺎران دﭼﺎر ﺷﻜﺴﺘﮕﻲ از ﻧﻮع ﭘﻨﺞ ﺑﻮدﻧﺪ .در ﻫﺸﺖ ﺑﻴﻤﺎر ﻓﻴﻜﺴﺎﺳﻴﻮن ﺑﺎ ﭘـﻴﭻ دﻳﻨﺎﻣﻴـﻚ ﻛﻨـﺪﻳﻼر
Dynamic Condylar Screw
) (DCSو در 12ﻧﻔﺮ دﻳﮕﺮ ﺑﺎ ﭘﻴﭻ دﻳﻨﺎﻣﻴﻚ ﻫﻴﭗ ) Dynamic Hip Screw (DHSاﻧﺠﺎم ﺷﺪ .ﺟﻮشﺧﻮردﮔﻲ در ﺗﻤﺎم ﺑﻴﻤﺎران *
دﻳﺪه ﺷﺪ .ﻫﻴﭻﻛﺪام از ﺑﻴﻤﺎران درد ﻳﺎ اﺧﺘﻼل ﺣﺮﻛﺖ ﻧﺪاﺷﺘﻨﺪ .ﻧﺘﻴﺠﻪﮔﻴﺮي :ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻧﺘﺎﻳﺞ ﺑﻪدﺳﺖ آﻣﺪه ،ﻧﻮﻳـﺴﻨﺪﮔﺎن ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،ﺑﻠﻮار ﻛﺸﺎورز ،ﺑﻴﻦ 16آذر و
ﻗﺪس ،ﺧﻴﺎﺑﺎن ﭘﻮرﺳﻴﻨﺎ ،داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان
ﺻﻔﺤﻪﮔﺬاري ﺳﺎب ﻣﺎﺳﻜﻮﻻر در ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ را ﭘﻴﺸﻨﻬﺎد ﻣﻲﻛﻨﻨﺪ.
ﺗﻠﻔﻦ021-88717358 :
E-mail: aghamirsalim@gmail.com
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﺷﻜـﺴﺘﮕﻲ ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ ،ﻓﻴﻜـﺴﺎﺳﻴﻮن
ﺑﻴﻮﻟﻮژﻳـﻚDynamic Hip ،Dynamic Condylar Screw ،
.Screw
ﺳﻤﺖ اﺳﺘﺨﻮان ﻛﻮرﺗﻴﻜﺎل ﺗﻨﻪ اﺳﺘﺨﻮان ران اداﻣﻪ دارد .ﺷﻜﺴﺘﮕﻲﻫـﺎي
ﻣﻘﺪﻣﻪ
ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ﻓﻤﻮر اﻏﻠﺐ ﻧﺘﻴﺠﻪ ﻳﻚ ﺗﺮوﻣـﺎ درﻣــﺎن ﺷﻜــﺴﺘﮕﻲﻫــﺎي ﺳــﺎبﺗﺮوﻛﺎﻧﺘﺮﻳــﻚ
(Subtrochantric 1
ﺑﺎ اﻧﺮژي ﺑﺎﻻ ﻣﻲﺑﺎﺷﻨﺪ 2.اﻳﻦ ﺷﻜﺴﺘﮕﻲﻫﺎ ﻣﻤﻜﻦ اﺳﺖ ﺑﻪ ﺳﻤﺖ ﻧـﻮاﺣﻲ 3
) fracturesﺑﺮاي ﺟﺮاﺣﺎن ارﺗﻮﭘﺪ ﺑﺴﻴﺎر ﭼﺎﻟﺶﺑﺮاﻧﮕﻴﺰ اﺳﺖ .اﻳﻦ ﻣﻨﻄﻘﻪ
ﺗﺮوﻛﺎﻧﺘﺮ ﺑﺰرگ ﻳﺎ اﻳﻨﺘﺮﺗﺮوﻛﺎﻧﺘﺮ ﮔﺴﺘﺮش ﻳﺎﺑﻨﺪ .ﺟﺎاﻧﺪازي ﺑﻪ روش ﺑـﺎز
ﺑﻴﻦ دو ﻧﺎﺣﻴﻪ ﻛﻪ ﻧﻴﺮوﻫﺎي ﺑـﺎ ﻓـﺸﺎر ﺑـﺎﻻ از ﻃـﺮف داﺧـﻞ و ﻧﻴﺮوﻫـﺎي
) (Open reductionﺑﻪ ﺗﻐﺬﻳـﻪ ﻋﺮوﻗـﻲ آﺳـﻴﺐ ﻣـﻲرﺳـﺎﻧﺪ ،ﻗﻄﻌـﺎت را
ﻛﺸﺸﻲ از ﻃﺮف ﺧﺎرج وارد ﻣﻲﺷﻮﻧﺪ ﻗﺮار دارد ﻛﻪ ﻣﻲﺗﻮاﻧﺪ ﻣﻨﺠـﺮ ﺑـﻪ
ﺗﻀﻌﻴﻒ ﻛﺮده و ﺑﺎﻓﺖﻫﺎي ﻧﺮم را آﺳﻴﺐ ﻣﻲزﻧﺪ ،ﻫـﻢﭼﻨـﻴﻦ ﻣـﻲﺗﻮاﻧـﺪ
ﻧﺎرﺳﺎﻳﻲ اﻳﻤﭙﻠﻨﺖﻫﺎ ﺷﻮد .اﻳﻦ ﻗﺴﻤﺖ از اﺳﺘﺨﻮان ﻳـﻚ ﻧﺎﺣﻴـﻪ اﻧﺘﻘـﺎﻟﻲ
4
ﺧﻄﺮ ﻋﺪم ﺟﻮشﺧﻮردن و ﻧﺎرﺳـﺎﻳﻲ اﻳﻤﭙﻠﻨـﺖ را ﻧﻴـﺰ اﻓـﺰاﻳﺶ دﻫـﺪ.
اﺳﺖ ﻛـﻪ از اﺳﺘﺨـﻮان اﺳﻔﻨﺠـﻲ ) (Cancellousﻧﺎﺣﻴـﻪ ﺗﺮوﻛﺎﻧﺘﺮﻳﻚ ﺑﻪ
ﺗﻜﻨﻴﻚﻫﺎي ﺟﺮاﺣﻲ ﺑﺎ اﺳﺘﻔﺎده از اﺑﺰارﻫـﺎي اﻳﻨﺘﺮاﻣـﺪوﻻري ﻛـﻢﺗـﺮ ﺑـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺳﻌﻴﺪرﺿﺎ ﻣﻬﺮﭘﻮر و ﻫﻤﻜﺎران
105
ﺑﺎﻓﺖﻫﺎي ﻧﺮم آﺳﻴﺐ ﻣﻲرﺳﺎﻧﻨﺪ 5.ﻃﺒـﻖ ﻣﻄﺎﻟﻌـﺎت ﻗﺒﻠـﻲ ،ﺗﻜﻨﻴـﻚﻫـﺎي
ﻣﻨﺎﺳﺐ اﻧﺠﺎم ﺷﺪ .اﻋﻤﺎل ﺟﺮاﺣﻲ ﻃﻲ دو ﺗـﺎ 13روز ﺑﻌـﺪ از ﭘـﺬﻳﺮش
ﻣﺬﻛﻮر ﺑﺮاي درﻣﺎن ﺷﻜﺴﺘﮕﻲﻫﺎي وﺳﻴﻊ ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ ﻛـﻪ ﻧﺎﺣﻴـﻪ
ﺻﻮرت ﮔﺮﻓﺖ .ﺑﻴﻤﺎران ﺑﺮاي ﺗﻌﻴﻴﻦ ﻣﻴﺰان درد ،ﻣﻴﺰان ﺣﺮﻛﺖ در ﻫﻴـﭗ
اﻳﻨﺘﺮﺗﺮوك را ﻧﻴﺰ درﮔﻴﺮ ﻧﻤﻮده اﺳﺖ ،ﻣﻨﺎﺳﺐ ﻧﻤﻲﺑﺎﺷﺪ .ﻫﻢﭼﻨـﻴﻦ اﻳـﻦ
و زاﻧﻮ ،دﻓﻮرﻣﻴﺘﻲﻫﺎي زاوﻳﻪاي و ﭼﺮﺧﺸﻲ و اﺧﺘﻼف ﻃﻮل ﭘﺎﻫﺎ و ﻧﻴـﺰ
ﺗﻜﻨﻴﻚﻫﺎ در ﺑﻌـﻀﻲ از ﺑﻴﻤـﺎران ﺑﺎﻋـﺚ ﺑـﻪ وﺟـﻮد آﻣـﺪن ﻋـﻮارض و
ﺟﻮشﺧﻮردﮔﻲ ﺑﺮاﺳﺎس ﻳﺎﻓﺘﻪﻫﺎي رادﻳﻮﮔﺮاﻓﻲ ﺑﺮرﺳﻲ ﺷﺪﻧﺪ.
ﻣﺸﻜﻼت ﻓﺮاوان ﺷﺪهاﻧﺪ7.و 6ﻳﻜﻲ دﻳﮕﺮ از ﺗﻜﻨﻴﻚﻫﺎي ﻣـﻮرد اﺳـﺘﻔﺎده،
ﺗﻜﻨﻴﻚ ﺟﺮاﺣﻲ :ﺑﻴﻤـﺎر ﺑـﻪ ﺻـﻮرت ﺧﻮاﺑﻴـﺪه ﺑـﻪ ﭘـﺸﺖ ﺑـﺮ روي
ﺟﺎاﻧــﺪازي ﺑــﻪ روش ﺑــﺴﺘﻪ ) (Closed reductionو ﺻــﻔﺤﻪﮔــﺬاري
Fracture tableﻗﺮار ﮔﺮﻓﺘﻪ و ﻋﻤﻞ Reductionاﻧﺠﺎم ﻣـﻲﺷـﻮد .ﺑـﺮش
ﺑﻴﻮﻟﻮژﻳﻚ ) (Biologic platingﻣﻲﺑﺎﺷﺪ ﻛﻪ از ﺑﺮش ﮔﺴﺘﺮده ﺑﺎﻓﺖ ﻧـﺮم
5cmﻟﺘﺮال ﺗﺮوﻛﺎﻧﺘﺮ ﺑﺰرگ اﻳﺠﺎد و ﻓﺎﺷﻴﺎي ﻋﻤﻘﻲ ﻛﻨﺎر زده ﻣﻲﺷﻮد .ﺑـﺎ
در درﻣﺎن ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌـﻪاي ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ ﺟﻠـﻮﮔﻴﺮي
OEC® fluoroscopic unit Plus, Salt Lake
ﻣﻲﻛﻨﺪ .ﺑﺮﺧﻼف Condylar blade plateﻛﻪ ﻧﻴـﺎز ﺑـﻪ ﻫـﻢ ﺗـﺮازي ﺳـﻪ
ﻛﻨﺘـﺮل ﻓﻠﻮﺋﻮروﺳـﻜﻮﭘﻲ Utah) C-Arm
(9800City,ﭘــﻴﻦ راﻫﻨﻤــﺎ در ﻗــﺴﻤﺖ ﭘﺮوﮔﺰﻳﻤــﺎل و
Dynamic
Condylar lag screwﺑﻪ وﺳﻴﻠﻪ ﻳﻚ ﮔﻴﺮه ﺳﻪ ﺷﺎﺧﻪ در ﻣﻜـﺎن ﻣـﺬﻛﻮر
Dynamic Hip Screw
ﻗﺮار داده ﺷﺪ .ﭘﻠﻴﺖ Barrelﺑﻪ اﻧـﺪازه ﭼﻬـﺎر ﺗـﺎ ﭘـﻨﺞ ﺳـﻮراخ ﭘـﻴﭻ در
) (DHSﺗﻨﻬﺎ ﻧﻴﺎز ﺑﻪ ﻫﻢ ﺗﺮازي دو ﺻﻔﺤﻪاي دارﻧﺪ و ﻛﺎرﮔﺰاري آن آﺳﺎن
ﻗﺴﻤﺖ دﻳﺴﺘﺎل ﺷﻜﺴﺘﮕﻲ ﻗﺮار ﮔﺮﻓﺖ .ﺳﭙﺲ در ﻗﺴﻤﺖ دﻳـﺴﺘﺎل ﻳـﻚ
ﻣﻲﺑﺎﺷﺪ 8.اﻳﻦ ﻣﻄﺎﻟﻌﻪ آﻳﻨﺪهﻧﮕﺮ در ﺑﺨﺶ ارﺗﻮﭘﺪي ﺑﻴﻤﺎرﺳﺘﺎن ﺷـﺮﻳﻌﺘﻲ
ﺑﺮش ﺻﻮرت ﮔﺮﻓﺖ )ﺷﻜﻞ .(1ﭘﻠﻴﺖ از ﻃﺮﻳﻖ ﺑـﺮش ﭘﺮوﮔﺰﻳﻤـﺎل ﺑـﻪ
اﻧﺠﺎم ﺷﺪ و ﻫﺪف آن ﺑﺮرﺳﻲ ﻓﻴﻜﺴﺎﺳﻴﻮن ﺑﻴﻮﻟﻮژﻳﻚ در ﺷﻜﺴﺘﮕﻲﻫﺎي
ﺻﻮرﺗﻲ ﻛﻪ Barrelﻫﺎ ﺑﻪ ﺳﻤﺖ ﺟﺮاح ﻗﺮار ﮔﻴﺮد وارد ﺳﺎﻳﺖ ﺷﻜﺴﺘﮕﻲ
ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎب ﺗﺮوﻛﺎﻧﺘﺮﻳﻚ ﻣﻲﺑﺎﺷﺪ.
ﺷﺪ .ﺳﭙﺲ ﭘﻼك 180درﺟﻪ ﭼﺮﺧﺎﻧﺪه ﺷﺪ ﺗﺎ در ﻣﻘﺎﺑﻞ اﺳـﺘﺨﻮان ﻗـﺮار
ﺻﻔﺤﻪاي ﺑﺮاي ﻓﻴﻜﺴﺎﺳﻴﻮن دارد ،ﺑﺎ ﭘﻴﭻ دﻳﻨﺎﻣﻴـﻚ ﻛﻨـﺪﻳﻼر ) Condylar Screw (DCSﻳﺎ ﭘﻴﭻ دﻳﻨﺎﻣﻴﻚ ﻫﻴﭗ
ﮔﻴﺮد .ﭘﺲ از اﻃﻤﻴﻨﺎن از ﻗﺮارﮔﻴﺮي ﭘﻼك در ﻣﻜﺎن ﻣﻨﺎﺳﺐ ،ﻫﻢ ﺗـﺮازي و ﻃﻮل ﭘﺎﻫﺎ ﭼﻚ ﺷﺪ .ﻫﻢﺗﺮازي ﭼﺮﺧﺸﻲ ) (Rotational alignmentﺑﻪ
روش ﺑﺮرﺳﻲ
وﺳﻴﻠﻪ Cortical step signﻳﺎ ﻣﻘﺎﻳﺴﻪ ﺷﻜﻞ ﺗﺮوﻛﺎﻧﺘﺮﻫﺎي ﻛﻮﭼﻚ ﻣـﻮرد
اﻳﻦ ﻣﻄﺎﻟﻌﻪ آﻳﻨﺪهﻧﮕﺮ در ﺑﺨﺶ ارﺗﻮﭘﺪي ﺑﻴﻤﺎرﺳﺘﺎن ﺷﺮﻳﻌﺘﻲ اﻧﺠـﺎم
ارزﻳﺎﺑﻲ ﻗﺮار ﮔﺮﻓﺘﻪ ﺷﺪ 11.ﻫﻢﭼﻨﻴﻦ ﺑـﺮاي ﺑـﻪدﺳـﺖ آوردن ﻫـﻢﺗـﺮازي
ﺷﺪ .در اﻳﻦ ﻣﻄﺎﻟﻌﻪ از ﻛﻤﻴﺘﻪ اﺧﻼق داﻧﺸﮕﺎه اﺟﺎزه ﮔﺮﻓﺘـﻪ و اﻃﻼﻋـﺎت
ﻃﻮل اﻧﺪامﻫﺎ ،اﻧﺪام آﺳﻴﺐ دﻳﺪه ﺑﺎ ﻃﻮل اﻧﺪام ﺳﺎﻟﻢ ﻣﻘﺎﻳﺴﻪ ﺷﺪ .ﭘﻼك ﺑﻪ
ﺑﻴﻤــﺎران ﺑــﻪ ﺻــﻮرت ﻣﺤﺮﻣﺎﻧــﻪ ﺑﺮرﺳــﻲ ﺷــﺪ .از ﺳــﺎل ،1385-1390
وﺳﻴﻠﻪ ﭼﻬﺎر ﺗﺎ ﭘﻨﺞ ﭘﻴﭻ در دﻳﺴﺘﺎل ﺷﻜﺴﺘﮕﻲ ﺛﺎﺑـﺖ ﮔـﺸﺖ .در ﻃـﻮل
20ﺑﻴﻤﺎر ﺑﺎ ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 25) 42/5ﺗﺎ 72ﺳﺎل( ﺑﺎ ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ
ﺟﺮاﺣﻲ ﻣﻜﺎن ﺷﻜﺴﺘﮕﻲ ﺗﺤﺖ ﻋﻤﻞ ﻣﺴﺘﻘﻴﻢ ﻗﺮار ﻧﮕﺮﻓـﺖ و درنﻫـﺎي
ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ﻓﻤﻮر ﺑﻪ ﺻﻮرت آﻳﻨﺪهﻧﮕﺮ ﺑﺮرﺳـﻲ
ﺟﺪاﮔﺎﻧﻪاي ﺑﺮاي زﺧﻢ ﭘﺮوﮔﺰﻳﻤﺎل و دﻳﺴﺘﺎل ﻗـﺮار داده ﺷـﺪ .در اوﻟـﻴﻦ
ﺷﺪﻧﺪ .ﺑﻴﻤﺎران در ﻃـﻮل ﻳـﻚ ﻫﻔﺘـﻪ ﺑﻌـﺪ از ﺗﺮوﻣـﺎ ﺗﺤـﺖ ﺟﺎاﻧـﺪازي
روز ﭘﺲ از ﻋﻤﻞ ،ورزش ﻋﻀﻼت ﭼﻬﺎر ﺳـﺮ و در روز دوم ﺣﺮﻛـﺎت
) (Reductionﻏﻴﺮ ﻣﺴﺘﻘﻴﻢ ﺑﺎ ﻓﻴﻜـﺴﺎﺳﻴﻮن DHSﻳـﺎ DCSﻗـﺮار ﮔﺮﻓﺘﻨـﺪ.
ﻣﻔﺎﺻﻞ ران و زاﻧﻮ و وزنﮔﺬاري ﺑﺮ روي ﭘﺎﻫﺎ در روز ﺳﻮم ﺗﻮﺻﻴﻪ ﺷﺪ.
ﺑﻴﻤﺎراﻧﻲ ﻛﻪ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺷﺮﻛﺖ داده ﺷﺪﻧﺪ دﭼﺎر ﻳﻚ ﺷﻜﺴﺘﮕﻲ ﺑﻴﻦ
ﻣﻌﺎﻳﻨﺎت دورهاي در ﻫﻔﺘﻪﻫﺎي ﭼﻬﺎرم ،ﻫﺸﺘﻢ 12 ،و 24ﺻﻮرت ﮔﺮﻓﺖ.
ﻗﺴﻤﺖ ﺗﺤﺘﺎﻧﻲ ﺗﺮوﻛﺎﻧﺘﺮ ﻛﻮﭼﻚ ﺗﺎ 5cmزﻳﺮ آن ﺷﺪه ﺑﻮدﻧﺪ .ﺷﻜﺴﺘﮕﻲ
ﭘﺲ از ﻇﻬﻮر ﻛﺎﻟﻮس در رادﻳﻮﮔﺮاﻓﻲ ﺑﻪ ﺑﻴﻤﺎر اﺟﺎزه وزنﮔـﺬاري ﻛﺎﻣـﻞ
ﺣﺪاﻗﻞ ﺷﺎﻣﻞ ﺳﻪ ﺗﻜﻪ ﺑﻮد .ﺑﻴﻤﺎران ﺑﺎ ﺷﻜﺴﺘﮕﻲﻫﺎي ﺑـﺎز و ﭘﺎﺗﻮﻟﻮژﻳـﻚ
داده ﺷﺪ .ارزﻳﺎﺑﻲ ﻧﻬﺎﻳﻲ ﻳﻚ ﺳﺎل ﭘﺲ از ﻋﻤﻞ ﺻﻮرت ﮔﺮﻓﺖ.
از ﻣﻄﺎﻟﻌﻪ ﻛﻨﺎر ﮔﺬاﺷﺘﻪ ﺷﺪﻧﺪ .رادﻳﻮﮔﺮاﻓﻲﻫﺎي ﻗﺪاﻣﻲ ﺧﻠﻔﻲ و ﻟﺘـﺮال از ﻫﻴﭗ ﺗﺎ زاﻧﻮ ﮔﺮﻓﺘﻪ و ﺷﻜﺴﺘﮕﻲﻫـﺎ ﺑﺮاﺳـﺎس ﻃﺒﻘـﻪﺑﻨـﺪيﻫـﺎي 9AOو 10Seinsheimerﻛﻼسﺑﻨﺪي ﺷﺪﻧﺪ .ﻗﺒﻞ از ﻋﻤﻞ ﺑﻴﻤﺎران ﺗﺤـﺖ ﻛـﺸﺶ
ﻳﺎﻓﺘﻪﻫﺎ
DVT
23ﺑﻴﻤﺎر ﺑﺎ ﺷﻜﺴﺘﮕﻲﻫـﺎي ﭼﻨـﺪ ﻗﻄﻌـﻪاي ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ در
) 40 LMWHﻣﻴﻠﻲﮔﺮم روزاﻧﻪ( ﺗﺠﻮﻳﺰ ﺷﺪ .ﻗﺒﻞ از ﻋﻤـﻞ رادﻳـﻮﮔﺮاﻓﻲ-
ﺑﻴﻤﺎرﺳﺘﺎن ﺷﺮﻳﻌﺘﻲ ﭘﺬﻳﺮﻓﺘﻪ ﺷﺪﻧﺪ .ﻳﻜـﻲ از ﺑﻴﻤـﺎران ﺑـﻪ ﻋﻠـﺖ ﺷـﺪت
ﻫﺎي ﻓﻤﻮر ﻣﻘﺎﺑﻞ ﺑﻪ ﻣﻨﻈﻮر ﺗﻌﻴﻴﻦ ﻣﺤـﻞ ورود و ﻃـﻮل ﭘـﻼك )ﭘﻠﻴـﺖ(
ﺿﺮﺑـﻪ ﺑـﻪ ﺳـﺮ ﻓـﻮت ﻛـﺮد و دو ﻧﻔـﺮ دﻳﮕﺮ در ﻃﻮل ﻣﻌﺎﻳﻨﺎت دورهاي
اﺳــﻜﻠﺘﻲ ﻗــﺮار ﮔﺮﻓﺘ ـﻪ و ﭘﺮوﻓﻴﻼﻛــﺴﻲ ﺗﺮوﻣﺒــﻮز ﻋــﺮوق ﻋﻤﻘــﻲ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺑﺮرﺳﻲ ﺗﻜﻨﻴﻚ biologic plateدر ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎب ﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ران
106
ﺟﺪول :1 -ارزﻳﺎﺑﻲ ﻧﻬﺎﻳﻲ ﻣﻮرد
ﺳﻦ
ﻧﻮع ﺷﻜﺴﺘﮕﻲ AO
Seinsheimer
ﻋﻠﺖ
ﻧﻮع
ﻣﻴﺰان ﺧﻮن ﻣﺪت زﻣﺎن اﺧﺘﻼف ﻃﻮل
ﻓﻴﻜﺴﺎﺳﻴﻮن از دﺳﺖ
ﻋﻤﻞ )دﻗﻴﻘﻪ(
اﻧﺪام
ﻣﻴﺰان
ﻫﻢﺗﺮازي
ﺣﺮﻛﺖ
دﻓﻮرﻣﻴﺘﻲ
ﻋﻤﻠﻜﺮد
ﭼﺮﺧﺸﻲ
زﻣﺎن ﭘﻲﮔﻴﺮي )ﻣﺎه(
رﻓﺘﻪ 1
64
32C
3B
اﻓﺘﺎدن
DHS
410
81
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
2
72
32C
4
اﻓﺘﺎدن
DCS
924
110
-
15درﺟﻪ
ﻧﺮﻣﺎل
ﻛﻢﺗﺮ از 10
ﺧﻮب
22
درﺟﻪ ﻛﺎﻫﺶ اﻛﺴﺘﻨﺸﻦ -
ﺧﻮب
12
ﻛﺎﻫﺶ ﻓﻠﻜﺸﻦ 3
29
32B
5
ﺗﺼﺎدف
DHS
742
91
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
4
47
32C
4
ﺗﺼﺎدف
DHS
650
63
1
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
5
45
32C
3B
ﺗﺼﺎدف
DHS
473
66
-
ﻧﺮﻣﺎل
ﭘﻨﺞ درﺟﻪ
6
32
32B
4
ﺗﺼﺎدف
DCS
410
70
-
ﻧﺮﻣﺎل
7
38
32B
4
ﺗﺼﺎدف
DCS
388
8
40
32C
4
ﺗﺼﺎدف
-
-
ﻋﺎﻟﻲ
18
ﻋﺎﻟﻲ
20
ﺧﻮب
28
واروس 67
2
ﻧﺮﻣﺎل
DHS
639
90
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل ﻧﺮﻣﺎل
-
ﭘﻨﺞ درﺟﻪ
ﻛﻢﺗﺮ از 10
واروس
درﺟﻪ ﻛﺎﻫﺶ
ﻋﺎﻟﻲ ﻋﺎﻟﻲ ﺧﻮب
15 16 21
اﻛﺴﺘﻨﺸﻦ 9
33
32C
5
ﺗﺼﺎدف
DHS
684
83
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
-
ﻋﺎﻟﻲ
20
10
47
32C
3a
ﺗﺼﺎدف
DCS
491
72
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
-
ﻋﺎﻟﻲ
14
11
25
32C
3B
ﺗﺼﺎدف
DHS
645
75
-
15درﺟﻪ
22درﺟﻪ
-
ﻣﺘﻮﺳﻂ
35
ﻛﺎﻫﺶ
واروس و
ﻓﻠﻜﺸﻦ
19درﺟﻪ ﻓﻠﻜﺸﻦ
12
30
32C
4
ﺗﺼﺎدف
DCS
1020
66
1/8
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
-
ﺧﻮب
30
13
41
32C
5
ﺗﺼﺎدف
DHS
396
74
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
-
ﻋﺎﻟﻲ
21
14
42
32C
5
ﺗﺼﺎدف
DHS
340
73
1/3
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
-
ﺧﻮب
19
15
40
32B
4
ﺗﺼﺎدف
DHS
895
125
-
ﻧﺮﻣﺎل
ﻧﺮﻣﺎل
ﻛﻢﺗﺮ از 10
ﺧﻮب
31
16
62
32C
5
اﻓﺘﺎدن
DHS
455
71
-
20درﺟﻪ
ﻧﺮﻣﺎل
17
31
32B
4
ﺗﺼﺎدف
DCS
743
73
-
18
32
32B
4
ﺗﺼﺎدف
DCS
390
19
49
32C
5
اﻓﺘﺎدن
DHS
860
20
51
32B
5
DCS
1125
درﺟﻪ ﻛﺎﻫﺶ اﻛﺴﺘﻨﺸﻦ -
ﺧﻮب
25
ﻛﺎﻫﺶ ﻓﻠﻜﺸﻦ 70 65 104
1/5 -
ﻧﺮﻣﺎل ﻧﺮﻣﺎل ﻧﺮﻣﺎل ﻧﺮﻣﺎل
ﻧﺮﻣﺎل ﻧﺮﻣﺎل ﻧﺮﻣﺎل ﻧﺮﻣﺎل
ﻛﻢﺗﺮ از 10
ﻋﺎﻟﻲ ﺧﻮب ﻋﺎﻟﻲ ﺧﻮب
14 16 29 23
درﺟﻪ ﻛﺎﻫﺶ اﻛﺴﺘﻨﺸﻦ DHS: Dynamic Hip Screw, DCS: Dynamic Condylar Screw, AO: Arbeitsgemeinschaft für Osteosynthese
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺳﻌﻴﺪرﺿﺎ ﻣﻬﺮﭘﻮر و ﻫﻤﻜﺎران
107
ﺷــﻜﻞ -A :1 -رادﻳــﻮﮔﺮاﻓﻲ ﻗﺒــﻞ از ﻋﻤــﻞ :ﺷﻜــﺴﺘﮕﻲﻫــﺎي ﭼﻨــﺪ ﻗﻄﻌــﻪاي ﺳــﺎبﺗﺮوﻛﺎﻧﺘﺮﻳــﻚ -B .در دو ﺑــﺮش ﻛﻮﭼــﻚ Submuscular plateدر ﻣﺤــﻞ ﺷﻜﺴﺘﮕﻲ ﻗﺮار داده ﻣﻲﺷﻮد -C .رادﻳﻮﮔﺮاﻓﻲ ﺑﻌﺪ از ﻋﻤﻞ -D .ﺟﻮشﺧﻮردن ﻛﺎﻣﻞ ﺷﻜﺴﺘﮕﻲ در رادﻳﻮﮔﺮاﻓﻲ ﺑﻌﺪ از ﺷﺶ ﻣﺎه.
ﺣﺎﺿﺮ ﺑﻪ اداﻣﻪ ﻫﻤﻜﺎري ﻧـﺸﺪﻧﺪ .ﺑﻨـﺎﺑﺮاﻳﻦ در ﻧﻬﺎﻳـﺖ 20ﺑﻴﻤـﺎر ﺑـﺮاي اﻧﺠﺎم اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺎﻗﻲ ﻣﺎﻧﺪﻧﺪ 16 .ﺑﻴﻤﺎر ﺑـﺮ اﺛـﺮ ﺗـﺼﺎدﻓﺎت ﺟـﺎدهاي و ﭼﻬﺎر ﺑﻴﻤﺎر ﺑﺮ اﺛﺮ اﻓﺘﺎدن از ارﺗﻔﺎع دﭼـﺎر ﺷﻜـﺴﺘﮕﻲ ﺷـﺪه ﺑﻮدﻧـﺪ .ﺑـﺮ اﺳﺎس ﻃﺒﻘﻪﺑﻨﺪي Seinheimerﭼﻬﺎر ﺑﻴﻤﺎر در ﺗﻴـﭗ ﺳـﻪ ﻗـﺮار داﺷـﺘﻨﺪ
ﺷﻜﻞ -A :2 -رادﻳﻮﮔﺮاﻓﻲ ﺑﻴﻤﺎر ﺷﻤﺎره -B ،11رادﻳﻮﮔﺮاﻓﻲ ﺑﻌـﺪ از ﻋﻤـﻞ ﺑﻴﻤـﺎر ﺷﻤﺎره -C ،11رادﻳﻮﮔﺮاﻓﻲ درﻣﺎن ﺑﻌﺪ از ﮔﺬﺷﺖ ﻳﻚ ﺳﺎل از ﻋﻤﻞ
)ﻳﻚ ﺑﻴﻤﺎر ﺗﻴﭗ 3Aو ﺳﻪ ﺑﻴﻤﺎر در ﺗﻴﭗ 9 ،(3Bﺑﻴﻤﺎر در ﺗﻴﭗ ﭼﻬﺎر و ﻫﻔﺖ ﺑﻴﻤﺎر در ﺗﻴﭗ ﭘﻨﺞ ﺷﻜﺴﺘﮕﻲ ﺑﻮدﻧـﺪ .ﺑـﻪ ﻃـﻮر ﻣﺘﻮﺳـﻂ ﺑﻴﻤـﺎران 22/5ﻣﺎه ) 12ﺗﺎ 35ﻣﺎه( ﺗﺤﺖ ﭘﻲﮔﻴﺮي درﻣﺎﻧﻲ ﻗـﺮار ﮔﺮﻓﺘﻨـﺪ .ﻫـﺸﺖ ﻣﻮرد از ﺑﻴﻤﺎران ﺗﺤﺖ درﻣﺎن DCSو 12ﻣﻮرد ﺗﺤـﺖ درﻣـﺎن ﺑـﺎ
DHS
ﭘﺎﻳﺎن ﺳﺎل اول ﺻﻮرت ﮔﺮﻓﺖ .ﺟﻮشﺧﻮردن ﺗﻤﺎم ﺑﻴﻤـﺎران در ﻧﻬﺎﻳـﺖ ﻣﺸﺎﻫﺪه ﺷﺪ )ﺷﻜﻞ ) (2ﺟﺪول .(1
ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﻃﻮل ﻣﺘﻮﺳﻂ ﺟﺮاﺣﻲ 79/4دﻗﻴﻘﻪ ) 60ﺗـﺎ 125دﻗﻴﻘـﻪ( و ﻣﻴﺰان ﻣﺘﻮﺳﻂ ﺧﻮنرﻳﺰي در ﺣﻴﻦ ﻋﻤﻞ 634ﻣﻴﻠﻲﻟﻴﺘﺮ ) 340ﺗـﺎ (1160 ﺑﻮد .ﻣﺘﻮﺳﻂ زﻣﺎن ﺟﻮشﺧﻮردن ﺷﻜﺴﺘﮕﻲﻫﺎ 19ﻫﻔﺘﻪ ﺑﻮد .ﭘﻨﺞ ﻧﻔـﺮ از
ﺑﺤﺚ
ﺑﻴﻤﺎران دﭼﺎر ﻋﺪم ﺗﻨﺎﺳﺐ ﻃﻮل اﻧﺪامﻫﺎ ﺷﺪﻧﺪ ﻛﻪ ﺑﻪ ﻃﻮر ﻣﻌﻤﻮل اﻧـﺪام
ﻣﻌﻤﻮﻻً ﺷﻜﺴﺘﮕﻲﻫﺎي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ ﺑﺮ اﺛﺮ ﺗﺮوﻣﺎﻫﺎي ﺑﺎ اﻧـﺮژي
ﺗﺤﺖ ﺟﺮاﺣﻲ 1/52cmﻛﻮﭼﻚﺗﺮ از اﻧﺪام ﺳﺎﻟﻢ ﺑﻮد ﻛﻪ اﻟﺒﺘﻪ ﻫﻴﭻﻛـﺪام
ﺑﺎﻻ در اﻓﺮاد ﺟﻮان رخ ﻣﻲدﻫﺪ .از ﻃﺮﻓﻲ اﻳﻦ ﻗﺴﻤﺖ از ﺑـﺪن در ﺑﺮاﺑـﺮ
از اﻳﻦ ﺑﻴﻤﺎران ﭘﺲ از ﺟﺮاﺣﻲ ﺑﻪ ﻋﻠـﺖ ﻋـﺪم ﺗﻨﺎﺳـﺐ اﻧـﺪامﻫـﺎ دﭼـﺎر
ﻧﻴﺮوﻫــﺎي ﻓــﺸﺎرﻧﺪه زﻳــﺎدي از ﻃــﺮف ﻗــﺴﻤﺖ داﺧــﻞ ﻗــﺮار دارد.
ﻟﻨﮕﻴﺪن ﻧﺸﺪﻧﺪ .دو ﻧﻔﺮ از ﺑﻴﻤـﺎران در ﺣـﺪود 20درﺟـﻪ واروس ﭘﻴـﺪا
ﺷﻜﺴﺘﮕﻲﻫﺎي اﻳﻦ ﻧﺎﺣﻴﻪ از ﺑﺪن ﻳﻜـﻲ از ﻣﻌـﻀﻼت درﻣـﺎن ﺑـﻪ ﻋﻠـﺖ
ﻛﺮده و ﻳﻜﻲ از ﺑﻴﻤﺎران ﻧﻴﺰ در ﻗـﺴﻤﺖ ﭘﺮوﮔﺰﻳﻤـﺎل ﺷﻜـﺴﺘﮕﻲ دﭼـﺎر
ﻣﻴﺰان ﺑﺎﻻي ﻋﻮارض ﻧﺎﺷﻲ از ﻋﻤﻞ ﻣﺎﻧﻨـﺪ ﻋـﺪم ﺟـﻮشﺧـﻮردﮔﻲ ،ﺑـﺪ 13
ﻓﻠﻜﺸﻦ دﻓـﻮرﻣﻴﺘﻲ ) (Anterior angulationﻗﻄﻌـﻪ ﭘﺮوﮔﺰﻳﻤـﺎل ﺷـﺪﻧﺪ،
ﺟــﻮشﺧــﻮردﮔﻲ ﺑــﻪ وﺳــﻴﻠﻪ ﺟﺮاﺣــﺎن ارﺗﻮﭘــﺪ ﻣــﻲﺑﺎﺷــﺪ .وﺳــﺎﻳﻞ
ﺷﺎﻳﺎن ذﻛﺮ اﺳﺖ ﻛﻪ ﻫﻴﭻﻛﺪام از اﻳﻦ دﻓﻮرﻣﻴﺘﻲﻫﺎ ﻣﻨﺠﺮ ﺑﻪ درد ﻳـﺎ ﻋـﺪم
اﻳﻨﺘﺮاﻣﺪوﻻري در درﻣﺎن اﻳـﻦ ﻧـﻮع از ﺷﻜـﺴﺘﮕﻲﻫـﺎ ﻧـﺴﺒﺖ ﺑـﻪ ﺳـﺎﻳﺮ
ﻛﺎراﻳﻲ اﻧﺪام ﻧﺸﺪه اﺳﺖ .ﻃﺒﻖ ﻣﻌﻴﺎرﻫﺎي 12Radfordآﺧﺮﻳﻦ ارزﻳﺎﺑﻲ در
ﺗﻜﻨﻴﻚﻫﺎ ﻣﺎﻧﻨﺪ DHSو DCSﻳﺎ Angle bladesﺑﻴﺶﺗﺮ ﻣﻮرد ﺗﻮﺟﻪ ﻗﺮار
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
Mehrpour et al. درbiologic plate ﺑﺮرﺳﻲ ﺗﻜﻨﻴﻚ ﻗﻄﻌﻪاي ﺳﺎب ﺗﺮوﻛﺎﻧﺘﺮﻳﻚ اﺳﺘﺨﻮان ران ﻫﺎي ﭼﻨﺪS. ﺷﻜﺴﺘﮕﻲ
108
ﺗﻨﻬﺎ روش ﺑﺴﻴﺎر آﺳﺎﻧﻲ ﻣـﻲﺑﺎﺷـﺪ ﺑﻠﻜـﻪ ﻧـﺴﺒﺖ ﺑـﻪ ﺳـﺎﻳﺮ روشﻫـﺎ از
ﺑﺮ اﺳﺎس ﻣﻄﺎﻟﻌﺎت ﻗﺒﻠﻲ ﻋﻮارض ﻧﺎﺷﻲ از ﻋﻤﻞ ﺑـﻪ وﺳـﻴﻠﻪ14.ﮔﺮﻓﺘﻪاﻧﺪ
ﻫـﻢﭼﻨـﻴﻦ،ﻛﻢﺗﺮﻳﻦ ﻣﻴﺰان ﺑﻬﺮهﮔﻴﺮي از ﻓﻠﻮروﺳﻜﻮﭘﻲ ﺑﺮﺧﻮردار اﺳـﺖ
ﻫـﻢﭼﻨـﻴﻦ15و16. از ﺑﻴﻤـﺎران رخ ﻣـﻲدﻫـﺪ%20 اﻳﻦ ﺗﻜﻨﻴﻚ در ﺑﻴﺶ از
،Pon-Cheng Lee .زﻣﺎن ﺟﺮاﺣﻲ ﺑﻪ ﻃﻮر ﻗﺎﺑﻞ ﺗﻮﺟﻬﻲ ﻛﺎﻫﺶ ﻣـﻲﻳﺎﺑـﺪ
ﻋﻮارض ﭘﺲ از ﻋﻤﻞ ﻣﺎﻧﻨﺪ ﺑﻴﺮونزدﮔﻲ ﭘﻴﭻﻫـﺎ از ﻧﺎﺣﻴـﻪ ﻟﺘـﺮال و ﻧﻴـﺰ
ﻛﺎراﻳﻲ ﺻﻔﺤﻪﮔـﺬاري ﺑﻴﻮﻟﻮژﻳـﻚ و ﻣـﻴﺦﮔـﺬاري درون اﺳـﺘﺨﻮاﻧﻲ را
ﻣﻬﺎﺟﺮت آنﻫﺎ ﺑﻪ داﺧﻞ ﻣﻔﺼﻞ و اﻳﺠـﺎد درد ﻓـﺮاوان و ﻛـﺎﻫﺶ ﻣﻴـﺰان
8
در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺎ ﺗﻮﺟـﻪ.ﻣﻘﺎﻳﺴﻪ و ﺗﻔﺎوت ﻣﻌﻨﻲداري را ﮔﺰارش ﻧﻜﺮد
ﺑﻴﻤـﺎران ﺗﺤـﺖ%20 15.ﺣﺮﻛﺎت از ﺳﺎﻳﺮ ﻋﻮارض اﻳﻦ ﺗﻜﻨﻴﻚ ﻣﻲﺑﺎﺷـﺪ
ﺑﻪ ﺑﻬﺒﻮدي ﻛﺎﻣﻞ ﺑﻴﻤﺎران و اﺳﺘﻔﺎده از وﺳﺎﻳﻞ ارزان ﻗﻴﻤﺖ و ﻫـﻢﭼﻨـﻴﻦ
14
ﻗﻮﻳﺎً ﺻﻔﺤﻪﮔﺬاري ﺳـﺎبﻣﺎﺳـﻜﻮﻻر را، ﻧﻮﻳﺴﻨﺪﮔﺎن،ﻛﺎﻫﺶ زﻣﺎن ﻋﻤﻞ
ﻣﻌﻤﻮﻻً اﻋﻤﺎل ﺟﺮاﺣﻲ ﻛﻪ ﺑﻪ ﺻﻮرت ﻣﺴﺘﻘﻴﻢ ﻣﻜﺎن ﺷﻜﺴﺘﮕﻲ را ﻫﺪف
ﺑﺮاي درﻣﺎن ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨـﺪ ﻗﻄﻌـﻪاي ﺳـﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ ﺗﻮﺻـﻴﻪ
ﻋﻮارﺿـﻲ ﻣﺎﻧﻨـﺪ،ﻗﺮار ﻣﻲدﻫﻨﺪ ﺑﻪ ﻋﻠﺖ در ﻣﻌﺮض ﻗﺮار دادن اﺳﺘﺨﻮان
اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﭘﺎﻳﺎنﻧﺎﻣـﻪ ﺑـﺎ ﻋﻨـﻮان "ﺑﺮرﺳـﻲ: ﺳﭙﺎﺳﮕﺰاري.ﻣﻲﻛﻨﻨﺪ
ﺷﻜــﺴﺘﮕﻲ دوﺑــﺎره و ﺗـﺄﺧﻴﺮ در ﺟــﻮشﺧــﻮردن را اﻓــﺰاﻳﺶ،ﻋﻔﻮﻧــﺖ
ﻧﺘﺎﻳﺞ درﻣﺎﻧﻲ ﺷﻜﺴﺘﮕﻲﻫﺎي ﭼﻨﺪ ﻗﻄﻌﻪاي ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳـﻚ اﺳـﺘﺨﻮان
ﻣـﻲﺗﻮاﻧـﺪDHS ﻳـﺎDCS ﺻﻔﺤﻪ ﮔﺬاري زﻳﺮ ﻋﻀﻼﻧﻲ ﻣﺎﻧﻨـﺪ17.ﻣﻲدﻫﺪ
ران ﺑﺎ روش ﻓﻴﻜﺴﺎﺳﻴﻮن ﺑﻴﻮﻟﻮژﻳﻚ در ﺑﻴﻤﺎران ﺗﺤﺖ ﻋﻤﻞ ﺟﺮاﺣﻲ در
ﻗـﺴﻤﺖ.ﮔﺰﻳﻨﻪ ﻣﻨﺎﺳﺒﻲ در درﻣﺎن اﻳـﻦ ﺷﻜـﺴﺘﮕﻲﻫـﺎي دﺷـﻮار ﺑﺎﺷـﺪ
" در ﻣﻘﻄــﻊ دﻛﺘــﺮاي1385-90 ﺑﻴﻤﺎرﺳــﺘﺎن ﺷــﺮﻳﻌﺘﻲ در ﺳــﺎلﻫــﺎي
ﺷﻜﺴﺘﮕﻲ ﭼﻨﺪ ﻗﻄﻌﻪاي ﺑﻪ ﺻﻮرت ﻣﺴﺘﻘﻴﻢ ﺑـﻪ وﺳـﻴﻠﻪ ﺻـﻔﺤﻪﮔـﺬاري
239 و ﻛــﺪ1390 ﺗﺨﺼــﺼﻲ ﺟــﺮاح اﺳــﺘﺨﻮان و ﻣﻔﺎﺻــﻞ در ﺳــﺎل
اﻣﺎ ﺗﻤﺎم ﺷﻜـﺴﺘﮕﻲﻫـﺎي ﺑﻴﻤـﺎران در اﻳـﻦ،ﺳﺎبﻣﺎﺳﻜﻮﻻر ﺛﺎﺑﺖ ﻧﺸﺪه
ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﺑﺎ ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه ﻋﻠـﻮم ﭘﺰﺷـﻜﻲ ﺗﻬـﺮان اﺟـﺮا90/7/10
. ﺗـﺮﻣﻴﻢ ﻛﺎﻣـﻞ ﻳﺎﻓﺘـﻪاﻧـﺪ،ﻣﻄﺎﻟﻌﻪ ﺑﺪون ﻧﻴﺎز ﺑﻪ ﮔﺮﻓﺖ ﻳﺎ ﺳﺎﻳﺮ درﻣﺎنﻫـﺎ
در اﻳﻦ ﻣﻘﺎﻟﻪ از ﻣﺮﻛﺰ رﺷﺪ اﺳﺘﻌﺪادﻫﺎي درﺧـﺸﺎن و ﻣﺮﻛـﺰ.ﺷﺪه اﺳﺖ
ﻋﻠــﺖ آن ﺣــﺪاﻗﻞ دﺳــﺖﻛــﺎري در ﺑﺎﻓــﺖﻫــﺎي اﻃــﺮاف ﺷﻜــﺴﺘﮕﻲ و
ﭘﮋوﻫﺶﻫـﺎي داﻧـﺸﺠﻮﻳﻲ داﻧـﺸﮕﺎه ﻋﻠـﻮم ﭘﺰﺷـﻜﻲ ﺗﻬـﺮان ﺑـﻪ ﻣﻨﻈـﻮر
اﺳــﺘﺨﻮان در ﺷﻜــﺴﺘﮕﻲﻫــﺎي ﻧﺎﺣﻴــﻪ.ﭘﺮﻳﻮﺳــﺖ اﺳــﺘﺨﻮان ﻣــﻲﺑﺎﺷــﺪ
.ﺣﻤﺎﻳﺖﻫﺎي اﻧﺠﺎم ﺷﺪه در اﻧﺠﺎم اﻳﻦ ﻃﺮح ﺗﻘﺪﻳﺮ و ﻗﺪرداﻧﻲ ﻣﻲﺷﻮد
اﻳﻦ روش ﻧﻪ.ﺳﺎبﺗﺮوﻛﺎﻧﺘﺮﻳﻚ ﻛﺎﻟﻮس ﺗﺸﻜﻴﻞ داده و ﺟﻮش ﻣﻲﺧﻮرد
.ﻋﻤﻞ ﻓﻴﻜﺴﺎﺳﻴﻮن اﻳﻨﺘﺮاﻣﺪوﻻري ﻧﻴﺎز ﺑﻪ ﻋﻤﻞ ﻣﺠـﺪد ﭘﻴـﺪا ﻣـﻲﻛﻨﻨـﺪ
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Seinsheimer F. Subtrochanteric fractures of the femur. J Bone Joint Surg Am 1978;60(3):300-6. Celebi L, Can M, Muratli HH, Yagmurlu MF, Yuksel HY, Bicimoğlu A. Indirect reduction and biological internal fixation of comminuted subtrochanteric fractures of the femur. Injury 2006;37(8):740-50. Siebenrock KA, Müller U, Ganz R. Indirect reduction with a condylar blade plate for osteosynthesis of subtrochanteric femoral fractures. Injury 1998;29 Suppl 3:C7-15. Kinast C, Bolhofner BR, Mast JW, Ganz R. Subtrochanteric fractures of the femur. Results of treatment with the 95 degrees condylar blade-plate. Clin Orthop Relat Res 1989;(238):122-30. Starr AJ, Hay MT, Reinert CM, Borer DS, Christensen KC. Cephalomedullary nails in the treatment of high-energy proximal femur fractures in young patients: a prospective, randomized comparison of trochanteric versus piriformis fossa entry portal. J Orthop Trauma 2006;20(4):240-6. Boldin C, Seibert FJ, Fankhauser F, Peicha G, Grechenig W, Szyszkowitz R. The proximal femoral nail (PFN): a minimal invasive treatment of unstable proximal femoral fractures: a prospective study of 55 patients with a follow-up of 15 months. Acta Orthop Scand 2003;74(1):53-8. Ertürer E, Tekkeşin M, Dirik Y, Aksoy B, Oztürk I. Radiographic and functional results of osteosynthesis with locked intramedulary nailing of subtrochanteric fractures of the femur. Acta Orthop Traumatol Turc 2004;38(4):265-9.
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Lee PC, Hsieh PH, Yu SW, Shiao CW, Kao HK, Wu CC. Biologic plating versus intramedullary nailing for comminuted subtrochanteric fractures in young adults: a prospective, randomized study of 66 cases. J Trauma 2007;63(6):1283-91. Müller ME, Nazarian S, Koch P, Schatzker J. The Comprehensive Classification of Fractures of Long Bones. New York: Springer; 1990. Seinsheimer F. Subtrochanteric fractures of the femur. J Bone Joint Surg Am 1978;60(3):300–306. Krettek C, Rudolf J, Schandelmaier P, Guy P, Könemann B, Tscherne H. Unreamed intramedullary nailing of femoral shaft fractures: operative technique and early clinical experience with the standard locking option. Injury 1996;27(4):233-54. Radford PJ, Howell CJ. The AO dynamic condylar screw for fractures of the femur. Injury 1992;23(2):89-93.. Bedi A, Toan Le T. Subtrochanteric femur fractures. Orthop Clin North Am 2004;35(4):473-83. Tencer AF, Johnson KD, Johnston DW, Gill K. A biomechanical comparison of various methods of stabilization of subtrochanteric fractures of the femur. J Orthop Res 1984;2(3):297-305. Pervez H, Parker MJ. Results of the long Gamma nail for complex proximal femoral fractures. Injury 2001;32(9):704-7. Kakkar R, Kumar S, Singh AK. Cephalomedullary nailing for proximal femoral fractures. Int Orthop 2005;29(1):21-4. Kinast C, Bolhofner BR, Mast JW, Ganz R. Subtrochanteric fractures of the femur. Results of treatment with the 95 degrees condylar blade-plate. Clin Orthop Relat Res 1989;(238):122-30.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺗﺸﺨﻴﺺ ﭘﺎﻳﺶ2012: دو روش104-109 ﻛﺎراﻳﻲ Tehran University Medical Journal; Vol. 70, No.ﺑﺮاي 2, May
Biological plating in comminuted subtrochanteric fractures
Abstract Saeedreza Mehrpour M.D.1 Mohamadreza Tavvafi M.D.1 Reza Sorbi2 Mohamad Reza Aghamirsalim2*
Received: January 01, 2012 Accepted: January 29, 2012
Background: Comminuted subtrochanteric fractures have been a challenge for orthopedic surgeons in terms of appropriate reduction and stable fixation. Numerous methods have been used for the fixation of comminuted subtrochanteric fractures
1- Department of Orthopaedic and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2- Medical Student, Students’ Scientific Research Center (SSRC), Exceptional Talent Development Center (ETDC), Tehran University of Medical Sciences, Tehran, Iran.
among which some are accompanied with technical difficulties and complications of their own. Regarding the results of previous studies, we decided to evaluate the biological fixation method in comminuted subtrochanteric fractures. Methods: In this prospective study, we evaluated 20 men with comminuted subtrochanteric femoral fractures. The patients underwent indirect reduction with dynamic hip screw (DHS) or dynamic condylar screw (DCS) fixation within one week of injury. The patients were evaluated clinically for pain, hip and knee range of motion, leg-length discrepancy and angular and rotational deformities, in addition the radiographic assessment of the union. Results: According to Seinsheimer's classification of subtrochanteric fractures, four patients had type III, nine had type IV and seven had type V fractures. Fracture fixation was performed by DCS in eight and by DHS in 12 cases. The average time of the operations was 79.4 (ranging from 60-125) minutes. Mean blood loss was 634 (ranging from 340-1160) milliliters. Uneventfully, union occurred in all patients with no clinical pain or dysfunction. Conclusion: Submuscular plating with either DCS or DHS is a viable option to treat comminuted subtrochanteric fractures. The results of this study highly suggest use of submuscular plating in the treatment of comminuted subtrochanteric fractures, especially in the third world countries.
*
Corresponding author: School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd., Tehran, Iran. Tel: +98- 21- 88717358 E-mail: aghamirsalim@gmail.com
Keywords: Biological fixation, dynamic condylar screw, dynamic hip screw, subtrochanteric fracture.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
زﻧﺎن110-118 ،1391 اردﻳﺒﻬﺸﺖ ﺷﻤﺎره 2 دوره ، ،70 ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﻋﻠﻮم ﻻﻛﺘﺎت ﻛﻮرﺗ،ﻴﺰول و آﻧﺪروژنﻫﺎ، ﺗﻬﺮان ،ﺑﺮ اﺳﺘﻘﺎﻣﺘﻲ ﻣﻘﺎوﻣﺘﻲ و ﭘﺰﺷﻜﻲ،ﺗﻤﺮﻳﻨﺎت ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﺗﺄﺛﻴﺮ
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ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﺑﺮ ﭘﺎﺳﺦ ﺣﺎد آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن ﻣﺴﻦ
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/06/26 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/09 :
دﻧﻴﺎ ﺻﻮرﺗﻲ ﺟﺎﺑﻠﻮ 1،ﺳﻴﺪ رﺿﺎ ﻋﻄﺎرزاده
ﭼﻜﻴﺪه
ﺣﺴﻴﻨﻲ *1،دﻻرام ﺻﻴﺎدﭘﻮر زﻧﺠﺎﻧﻲ،
2
زﻣﻴﻨﻪ و ﻫﺪف :ﺑﺎ اﻓﺰاﻳﺶ ﺳﻦ زﻧﺎن ﺑﻪ ﺗﺪرﻳﺞ ﺳﻄﺢ ﭘﺎﻳﻪ آﻧﺪروژنﻫﺎ ﻛﺎﻫﺶ ﻣﻲﻳﺎﺑﺪ ،ﻛﻪ ﻣﻤﻜﻦ اﺳﺖ ﺳـﺒﺐ ﺧـﺴﺘـﮕﻲ،
1
اﻣﻴﻦ اﺣﻤﺪي
ﻛﺎﻫﺶ ﻗﺪرت ﻋﻀﻼﻧﻲ و ﺗﺮاﻛﻢ اﺳﺘﺨﻮان ﺷﻮد .ﺑﻪ ﻫﻤﻴﻦ ﻣﻨﻈﻮر اﻳﻦ ﺗﺤﻘﻴﻖ ﺑﺎ ﻫﺪف ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻨﺎت ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ -1ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي ورزﺷﻲ داﻧﺸﻜﺪه ﺗﺮﺑﻴﺖ
ﺑﺮ ﭘﺎﺳﺦﻫﺎي ﺣﺎد آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن ﻣﺴﻦ اﻧﺠﺎم ﺷﺪ .روش ﺑﺮرﺳﻲ 10 :زن ﻣﺴﻦ ﺑﺎ ﻣﻴـﺎﻧﮕﻴﻦ ﺳـﻦ
ﺑﺪﻧﻲ و ﻋﻠﻮم ورزﺷﻲ داﻧﺸﮕﺎه ﻓﺮدوﺳﻲ ﻣﺸﻬﺪ،
54/30±3/74ﺳﺎل و ﻧﻤﺎﻳﻪ ﺗﻮده ﺑﺪن 24/88±2/07ﻛﻴﻠﻮﮔﺮم ﻣﺘﺮﻣﺮﺑﻊ ﺑﻪ ﻃﻮر ﺗﺼﺎدﻓﻲ در ﻳﻚ ﺟﻠﺴﻪ ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ،
ﻣﺸﻬﺪ ،اﻳﺮان. -2ﮔﺮوه ﭘﺎﺗﻮﻟﻮژي ،ﻣﺮﻛﺰ ﻓﺮﻫﻨﮕﻲ ﺗﺤﻘﻴﻘﺎﺗﻲ ﻋﻠﻤﻲ ﺟﻬﺎد داﻧﺸﮕﺎﻫﻲ اﻳﺮان ،ﻣﺸﻬﺪ ،اﻳﺮان.
اﺳﺘﻘﺎﻣﺘﻲ و ﻳﻚ ﺟﻠﺴﻪ اﺳﺘﺮاﺣﺖ ﺷﺮﻛﺖ ﻛﺮدﻧﺪ .ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ 45دﻗﻴﻘﻪ ،ﺷﺎﻣﻞ :ﺳﻪ ﺳﺖ 10ﺗﻜﺮاري ﻫﺸﺖ ﺣﺮﻛـﺖ وزﻧﻪ ﺗﻤﺮﻳﻨﻲ ﺑﺎ %80ﻳﻚ ﺗﻜﺮار ﺑﻴﺸﻴﻨﻪ ﺑﻮد .ﺗﻤـﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ 45دﻗﻴﻘـﻪ ﻓﻌﺎﻟﻴـﺖ روي دوﭼﺮﺧـﻪ ﻛﺎرﺳـﻨﺞ ﺑـﺎ ﺷـﺪت %60-%70ﺣﺪاﻛﺜﺮ اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ ﺑﻮد .در ﺟﻠﺴﻪ اﺳﺘﺮاﺣﺖ )ﻛﻨﺘﺮل( 45دﻗﻴﻘﻪاي ﻫﻴﭻ ﻓﻌﺎﻟﻴﺘﻲ اﻧﺠـﺎم ﻧﻤـﻲﮔﺮﻓـﺖ .از اﻓﺮاد ﻗﺒﻞ ،ﺑﻼﻓﺎﺻﻠﻪ و 15دﻗﻴﻘﻪ ﺑﻌﺪ از ﺗﻤﺮﻳﻦ و اﺳﺘﺮاﺣﺖ ،ﻧﻤﻮﻧـﻪﮔﻴـﺮي ﺧـﻮﻧﻲ ﮔﺮﻓﺘـﻪ ﺷـﺪ و ﻣﻘـﺎدﻳﺮ آﻧـﺪروژنﻫـﺎ، ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت ﺳﺮم اﻧﺪازهﮔﻴﺮي ﺷﺪﻧﺪ .ﻧﺘﺎﻳﺞ ﺑﺎ اﺳﺘﻔﺎده از روش اﻧﺪازهﮔﻴﺮيﻫـﺎي ﺗﻜـﺮاري در ﺳـﻄﺢ ﻣﻌﻨـﻲداري P<0/05ﺗﺠﺰﻳﻪ و ﺗﺤﻠﻴﻞ ﺷﺪﻧﺪ .ﻳﺎﻓﺘﻪﻫﺎ :ﺗﻐﻴﻴﺮات درون ﮔﺮوﻫﻲ ﺳﻄﻮح اﻓﺰاﻳﺶ ﻳﺎﻓﺘﻪ ﺗﺴﺘﻮﺳﺘﺮون ﭘﺲ از ﻣﺪاﺧﻠـﻪ ﻳـﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﻣﻌﻨﻲدار ﺑﻮد ) .(P<0/05ﻧﺘﺎﻳﺞ ﻧﺸﺎن داد ﭘﺲ از ﻣﺪاﺧﻠﻪ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ ﺳﻄﺢ دﻫﻴﺪرواﭘﻲاﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت اﻓﺰاﻳﺶ ﻣﻌﻨﻲدار ﻳﺎﻓﺖ ) .(P<0/05در ﺣﺎﻟﻲ ﻛـﻪ ﺗﻐﻴﻴـﺮات درون ﮔﺮوﻫـﻲ ﻣﻘـﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﮔﺮوهﻫﺎ ﻣﻌﻨﻲدار ﻧﺒﻮد ) ،(P>0/05ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﮔـﺮوهﻫـﺎ ﻣﻌﻨـﻲدار ﺑـﻮد ).(P<0/05
*
ﻧﺘﻴﺠﻪﮔﻴﺮي :ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﻣﻲﺗﻮاﻧﺪ ﺳﻄﻮح آﻧﺪروژنﻫـﺎ را در زﻧـﺎن ﻣـﺴﻦ اﻓـﺰاﻳﺶ دﻫـﺪ و از اﻳـﻦ ﻧﻈـﺮ ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﻣﺸﻬﺪ ،ﻣﻴﺪان آزادي ،ﭘﺮدﻳﺲ داﻧﺸﮕﺎه
ﻓﺮدوﺳﻲ ،داﻧﺸﻜﺪه ﺗﺮﺑﻴﺖ ﺑﺪﻧﻲ و ﻋﻠﻮم ورزﺷﻲ
ﻣﻲﺗﻮاﻧﺪ ﺑﺮاي ﺳﻼﻣﺖ و ﺗﻨﺪرﺳﺘﻲ آنﻫﺎ ﺿﺮوري ﺑﺎﺷﺪ.
ﺗﻠﻔﻦ0511-8934474 : E-mail: attarzadeh@um.ac.ir
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :آﻧﺪروژنﻫﺎ ،ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،ﺳﻼﻣﺖ ،زﻧﺎن ﻣﺴﻦ.
ﻣﻘﺪﻣﻪ
ﻛﺎﻫـﺶ ﻗـﺪرت ﻋﻀﻼﻧـﻲ ،ﺗﺮاﻛﻢ اﺳﺘﺨﻮاﻧﻲ ،ﺗﻤﺮﻛــﺰ و ﻣﻴـﻞ ﺟﻨـﺴﻲ 6و2
ﺷﺪه و ﻣﻮﺟﺒﺎت اﺣﺴﺎس ﺧﺴﺘـﮕﻲ و اﻓﺴـﺮدﮔﻲ را ﻓﺮاﻫﻢ ﻣﻲﺳﺎزد. زﻧﺎن ﺑﺎ اﻓﺰاﻳﺶ ﺳﻦ ﺗﻐﻴﻴــﺮات ﻗﺎﺑـﻞ ﺗـﻮﺟﻬﻲ در ﻋﻤﻠﻜــﺮد ﻏـﺪد
اﻋﺘﻘﺎد ﺑﺮ اﻳﻦ اﺳﺖ ﻛﻪ آﻧﺪروژنﻫﺎ ﺑﻪ ﻃﻮر ﻋﻤﺪه ﻣﺘﺎﺑﻮﻟﻴـﺴﻢ اﺳﺘﺨــﻮان
درونرﻳﺰ ) (Endocrineﺗﺠـﺮﺑﻪ ﻣﻲﻛﻨﻨﺪ ﻛﻪ ﻣﻮﺟﺐ ﻣﻲﺷﻮد در ﻣﻌـﺮض
را ﺗﻨﻈﻴـﻢ ﻣﻲﻛﻨﻨﺪ ،ﺑـﻪ ﻋـﻼوه ﻧﻘـﺶ آنﻫـﺎ ﺑـﻪ وﻳـﮋه ﺗـﺴﺘﻮﺳﺘﺮون در 8و7
ﻋﻼﻳﻢ و ﻣﺸﻜﻼت ﺟﺴﻤﻲ و رواﻧﻲ ﻣﺘﻌﺪدي ﭼﻮن :ﮔُﺮﮔﺮﻓﺘﮕﻲ ،ﭘـﻮﻛﻲ
ﭘﻴﺸﮕﻴﺮي از ﻛﺎﻫﺶ ﺗﻮده اﺳﺘﺨﻮاﻧﻲ،
اﺳﺘﺨﻮان ،ﺑﻴﻤﺎريﻫـﺎي ﻗﻠﺒـﻲ -ﻋﺮوﻗـﻲ ،ﻓـﺸﺎرﻫﺎي رواﻧـﻲ ،ﺧـﺴﺘﮕﻲ،
10و9
ﺧـﻮن 7،ارﺗﻘﺎي ﺳﻼﻣﺘـﻲ ،ﺷﺎدﻛـﺎﻣﻲ و ﻣﻴﻞ ﺟﻨﺴﻲ ﻧﻴﺰ ﻣﻬـﻢ اﺳـﺖ.
ﺗﺤﺮﻳﻚ ﭘﺬﻳﺮي ،ﻋﺼﺒﺎﻧﻴﺖ ،اﺿﻄﺮاب و اﻓﺴﺮدﮔﻲ ﻗﺮار ﻣﻲﮔﻴﺮﻧﺪ 1-3.ﺑـﺎ
ﺗﺤﻘﻴﻘﺎت ﻧﺸﺎن دادهاﻧﺪ ﻛﻪ ﺳﻄـﻮح ﭘﺎﻳﻴﻦ ﺗﺴﺘﻮﺳﺘﺮون ﻋﺎﻣـﻞ ﻣﺤــﺪود
اﻓــــﺰاﻳﺶ ﺳــــﻦ ،ﺳــــﻄﻮح آﻧــــﺪروژنﻫــــﺎ )ﺗــــﺴﺘﻮﺳﺘﺮون و
ﻛﻨﻨﺪه ﻗﺪرت و رﺷﺪ ﻋﻀﻼﻧﻲ در زﻧـﺎن ﻣـﺴﻦ اﺳـﺖ 5.اﮔﺮﭼـﻪ ﻣﻘـﺪار
دﻫﻴـﺪرواﭘـﻲآﻧـﺪروﺳﺘﺮون ﺳﻮﻟﻔﺎت( زﻧﺎن ﻛﺎﻫﺶ ﻣﻲﻳﺎﺑﺪ5و 4ﻛﻪ ﺑﺎﻋـﺚ
ﺗﺴﺘﻮﺳﺘﺮون در زﻧﺎن ﻳﻚ دﻫـﻢ ﻣﻘـﺪار آن در ﻣـﺮدان اﺳـﺖ12،و11و 7اﻣـﺎ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
اﻓﺰاﻳــﺶ ﮔﻠﺒــﻮلﻫـﺎي ﻗﺮﻣــﺰ
دﻧﻴﺎ ﺻﻮرﺗﻲ ﺟﺎﺑﻠﻮ و ﻫﻤﻜﺎران
111
ﻫﻤﻴﻦ ﻣﻘﺪار ﻛﻢ ،در ﻓﺮاﻳﻨﺪﻫﺎي ﻣﺘﺎﺑﻮﻟﻴﻜﻲ و ﻣﻴﻞ ﺟﻨﺴﻲ ﻧﻘﺶ ﻣﺤـﻮري
ﺳـــﻨﻲ اﻓـــﺰاﻳﺶ ﻳﺎﻓـــﺖ ،اﻣـــﺎ اﻓـــﺰاﻳﺶ در ﺳـــﻄﻮح ﻫﻮرﻣـــﻮن
دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت ﻧﻴﺰ ﻓﺮاوانﺗـﺮﻳﻦ آﻧـﺪروژن در
دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺗﻨﻬﺎ ﺑﻌﺪ از ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﻣـﺸﺎﻫﺪه
9و6
دارد.
13
ﮔﺮدش ﺧﻮن ﻣﺮدان و زﻧﺎن اﺳـﺖ ﻛـﻪ از ﻏـﺪه ﻓـﻮق ﻛﻠﻴـﻮي ﺗﺮﺷـﺢ
ﺷﺪ .آنﻫﺎ ﮔﺰارش دادﻧﺪ ﻛـﻪ ﺳـﻄﺢ ﻛـﻮرﺗﻴﺰول ﻃـﻲ ﺟﻠـﺴﺎت ﺗﻤـﺮﻳﻦ
ﻣﻲﺷﻮد 14.دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون و ﺳﻮﻟﻔﺎت آن ذﺧﺎﻳﺮ ﺑﺎﻟﻘﻮهاي ﻫﺴﺘﻨﺪ
ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﻛـﺎﻫﺶ ﻣﻌﻨـﻲداري ﻳﺎﻓـﺖ ،اﻟﺒﺘـﻪ اﻳـﻦ ﻛـﺎﻫﺶ در
ﻛﻪ ﻣﻲﺗﻮاﻧﻨﺪ در ﺑﺎﻓـﺖﻫـﺎي ﻣﺤﻴﻄـﻲ ﻣﺎﻧﻨـﺪ ﻣﻐـﺰ ،اﺳـﺘﺨﻮان ،ﺳـﻴﻨﻪ و
ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﻛﻢﺗﺮ ﺑﻮد .ﻫﻢﭼﻨﻴﻦ ﺳﻄﻮح ﻻﻛﺘﺎت ﺧﻮن ﻧﻴﺰ ﺗﻨﻬـﺎ ﺑﻌـﺪ
ﺗﺨﻤﺪانﻫﺎ ﺑﻪ ﺗﺴﺘﻮﺳﺘﺮون ﺗﺒـﺪﻳﻞ ﺷـﻮﻧﺪ15.و 13دﻫﻴـﺪرواﭘﻲآﻧﺪرﺳـﺘﺮون
از ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ در ﻫﻤﻪ ﮔﺮوهﻫﺎ اﻓﺰاﻳﺶ ﻣﻌﻨﻲداري داﺷﺖ اﻣﺎ ﻣﻘﺎدﻳﺮ
ﺳــﻮﻟﻔﺎت ) ،(DHEASﺑــﺎ اﻓــﺰاﻳﺶ ﺗـــﻮده ﺑــﺪون ﭼـــﺮﺑﻲ و داﻧــﺴﻴﺘـﻪ
اﻳــﻦ اﻓــﺰاﻳﺶ در زﻧــﺎن ﻣﻴــﺎنﺳــﺎل ﺑــﻴﺶﺗــﺮ از زﻧــﺎن ﻣــﺴﻦ ﺑــﻮد 5.در
اﺳﺘﺨـﻮان ،ﻛﻴﻔﻴـﺖ زﻧﺪﮔـﻲ زﻧﺎن را اﻓﺰاﻳـﺶ داده 5و ﺑﺮ ﻣﻴـﻞ ﺟﻨـﺴﻲ،
ﺗﺤﻘﻴﻘﻲ Hakkinenﭘﺎﺳﺦ ﺣﺎد ﻫﻮرﻣﻮنﻫﺎي ﺗـﺴﺘﻮﺳﺘﺮون و ﻛـﻮرﺗﻴﺰول
ﺳﻄﺢ اﻧﺮژي و ﺣﺴﺎﺳﻴﺖ اﻧـﺴﻮﻟﻴﻨﻲ ﺗـﺄﺛﻴﺮ ﻣﻄﻠـﻮب دارد 16.از ﻃﺮﻓـﻲ،
ﺑﻪ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﺷـﺪﻳﺪ را روي ﻫﻔـﺖ زن ﻣﻴـﺎنﺳـﺎل ﺑـﺎ
ﻣﺤﻘﻘﻴﻦ ﻧـﺸﺎن دادهاﻧـﺪ ﻛـﻪ ﺑـﻴﻦ ﺳـﻄﻮح DHEASو ﺑﻴﻤـﺎري ﺷـﺮﻳﺎن
ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 50ﺳﺎل و ﻫﺸﺖ زن ﻣـﺴﻦ ﺑـﺎ ﻣﻴـﺎﻧﮕﻴﻦ ﺳـﻨﻲ 70ﺳـﺎل
ﻛﺮوﻧﺮي ارﺗﺒﺎط ﻣﻌﻜﻮس وﺟﻮد دارد 17.ﺟﺪاي از اﻳﻦ ﺗﻐﻴﻴﺮات ،ﺗﻮأم ﺑـﺎ
ﺑﺮرﺳﻲ ﻛﺮد .ﻧﺘﺎﻳﺞ ﺗﺤﻘﻴﻖ ﺗﻐﻴﻴﺮ ﻣﻌﻨﻲداري در ﺳـﻄﻮح ﺗـﺴﺘﻮﺳﺘﺮون و
اﻓﺰاﻳﺶ ﺳﻦ ،ﺳﻄﺢ ﭘﺎﻳﻪ ﻫﻮرﻣﻮن ﻛﺎﺗﺎﺑﻮﻟﻴﻚ ﻛـﻮرﺗﻴﺰول زﻧـﺎن اﻓـﺰاﻳﺶ
ﻛﻮرﺗﻴﺰول ﻧﺸﺎن ﻧﺪاد 25.در ﺗﺤﻘﻴﻘـﻲ ﻛـﻪ Johnsonروي 16زن ﻳﺎﺋـﺴﻪ
ﻣﻲﻳﺎﺑﺪ 5.ﻛﺎﻫﺶ ﻧﺴﺒﺖ ﻫﻮرﻣﻮنﻫﺎي آﻧﺎﺑﻮﻟﻴﻚ ﺑـﻪ ﻛﺎﺗﺎﺑﻮﻟﻴـﻚ در اﻓـﺮاد
اﻧﺠــــﺎم داد ،اﻓــــﺰاﻳﺶ ﻣﻘــــﺎدﻳﺮ دﻫﻴــــﺪرواﭘﻲآﻧﺪرﺳــــﺘﺮون و
ﻣﺴﻦ ﻣﻤﻜﻦ اﺳﺖ ﺑﺎ ﻛﺎﻫﺶ ﻗﺪرت و اﻓﺖ ﺑﺎر ارﺗﺒﺎط داﺷـﺘﻪ ﺑﺎﺷـﺪ .در
دﻫﻴﺪرواﭘﻲ آﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت را ﺑﻪ دﻧﺒﺎل ﻣﺪاﺧﻠﻪ 30دﻗﻴﻘـﻪ ﻓﻌﺎﻟﻴـﺖ
واﻗﻊ ﻧﺴﺒﺖ آﻧﺪروژنﻫـﺎ ﺑـﻪ ﻛـﻮرﺗﻴﺰول ﺑﻴـﺎنﻛﻨﻨـﺪه ﺗﻌـﺎدل ﻣﺘﺎﺑﻮﻟﻴـﺴﻢ
26
روي ﺗﺮدﻣﻴﻞ ﺑﺎ %80ﺣﺪاﻛﺜﺮ اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ ﻣﺸﺎﻫﺪه ﻛﺮد.
آﻧﺎﺑﻮﻟﻴﻚ و ﻛﺎﺗﺎﺑﻮﻟﻴﻚ ﻋﻀﻠﻪ اﺳـﺖ 18.آﻧـﺪروژنﻫـﺎ و ﻛﻮرﺗﻴــﺰول ﺑـﻪ
ﺑﻪ ﻃﻮر ﺧﻼﺻﻪ ،ﮔﺮﭼﻪ زﻧﺎن ﻣﺴﻦ اﺧﺘﻼﻻت اﻧـﺪوﻛﺮﻳﻦ زﻳـﺎدي را
ﻋﻨـﻮان ﻣﻬﻢﺗﺮﻳﻦ ﺗﻨﻈﻴﻢﻛﻨﻨـﺪهﻫـﺎ در ﺳـﺎزﮔﺎري ﺑـﻪ ﺗﻤﺮﻳﻨــﺎت ﻗـﺪرﺗﻲ
ﺗﺠﺮﺑﻪ ﻣﻲﻛﻨﻨﺪ اﻣﺎ در راﺑﻄﻪ ﺑﺎ ﭘﺎﺳﺦ آﻧﺪروژنﻫﺎ ،ﻛـﻮرﺗﻴﺰول و ﻻﻛﺘـﺎت
ﻣﻄﺮح ﻣﻲﺑﺎﺷﻨﺪ 19.ﻳﻜﻲ از روشﻫﺎي اﻓﺰاﻳﺶ ﺗﻮده ﻋـﻀﻼﻧﻲ در اﻓـﺮاد
آنﻫﺎ ﺑﻪ ﺗﻤﺮﻳﻦ اﻃﻼﻋـﺎت ﻣﺤـﺪودي در دﺳـﺖ اﺳـﺖ .ﺑـﺎ اﻳـﻦ ﺣـﺎل
ﻣﺴﻦ ،ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ اﺳﺖ 20.ﺗﺤﻘﻴﻘﺎت ﻧﺸﺎن دادهاﻧﺪ ﺣﺘﻲ ﻳﻚ ﺟﻠﺴﻪ
ﺗﺤﻘﻴﻘﺎت اﻧﺪﻛﻲ ﻛﻪ ﭘﺎﺳﺦ آﻧﺪروژنﻫﺎ را در زﻧﺎن ﻣﺴﻦ ﺑﺮرﺳﻲ ﻛﺮدهاﻧـﺪ
ﺗﻤﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ ﻣـﻲﺗﻮاﻧـﺪ آﻏـﺎزﮔﺮ ﻓﺮاﻳﻨـﺪﻫﺎي ﺳـﺎزﮔﺎري در ﻋـﻀﻠﻪ
ﻧﺘﺎﻳﺞ ﻣﺘﻨﺎﻗﺼﻲ داﺷﺘﻪ اﺳﺖ ،ﺑﻪ ﻃﻮري ﻛﻪ ﺑﻌﻀﻲ از آنﻫﺎ ﺑﻼﻓﺎﺻﻠﻪ ﭘﺲ
اﺳﻜﻠﺘﻲ ﺑﺎﺷﺪ 21.زﻳﺮا اﻓﺰاﻳﺶ ﺣﺎد ﻫﻮرﻣﻮنﻫﺎي آﻧﺎﺑﻮﻟﻴﻚ ﻃـﻲ ﺗﻤـﺮﻳﻦ،
از ﻣﺪاﺧﻠﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ اﻓﺰاﻳﺶ ﺗﺴﺘﻮﺳﺘﺮون را ﮔـﺰارش
ﻣــﻲﺗﻮاﻧــﺪ ﻣﺤــﺮك ﻓﺮاﻳﻨــﺪﻫﺎي ﺳــﺎزﮔﺎري ﻣــﺮﺗﺒﻂ ﺑــﺎ اﻓــﺰاﻳﺶ ﺳــﻨﺘﺰ
25و24
ﻛﺮدﻧﺪ 5و ﺑﺮﺧﻲ دﻳﮕﺮ از ﺗﺤﻘﻴﻘﺎت ﺗﻐﻴﻴﺮي را ﻧﺸﺎن ﻧﺪاﻧﺪ.
ﭘﺮوﺗﻴﻴﻦﻫﺎي ﻋـﻀﻠﻪ ﺑﺎﺷـﺪ 22.ﺑـﺎ اﻳـﻦ ﻛـﻪ ﺑـﻪ ﻧﻈـﺮ ﻣـﻲرﺳـﺪ ﺳـﻄﻮح
از آنﺟﺎ ﻛﻪ ﺣﻔﻆ ﺑﻬﻴﻨﻪ ﺳﻄﻮح آﻧﺪروژنﻫـﺎ و ﻛـﻮرﺗﻴﺰول در زﻧـﺎن
آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت اﻓﺮاد ﺟﻮان ﺗﺤﺖ ﺗـﺎﺛﻴﺮ ﺗﻤـﺮﻳﻦ ﻗـﺮار
ﻣﺴﻦ ﺑﻴﺎنﻛﻨﻨﺪه ﺗﻌﺎدل ﻣﺘﺎﺑﻮﻟﻴﺴﻢ آﻧﺎﺑﻮﻟﻴﻚ و ﻛﺎﺗﺎﺑﻮﻟﻴﻚ ﻋـﻀﻠﻪ اﺳـﺖ و
ﻣﻲﮔﻴﺮد ،اﻣﺎ ﺗﻮاﻓﻖ ﻧﻈﺮ درﺑﺎره ﻫﻤﻴﻦ ﺗﻐﻴﻴﺮات در اﻓـﺮاد ﻣـﺴـﻦ وﺟـﻮد
وﺟﻮد ارﺗﺒﺎط ﻣﺴﺘﻘﻴﻢ ﻣﻴﺎن آن دو ﺑﺎ ﺳﻄﺢ ﻣﻘﻄـﻊ و ﻗـﺪرت ﻋـﻀﻠﻪ ﺑـﻪ
ﻧﺪارد23.و 19ﺷﺎﻳﺪ ﭘﺎﺳﺦ آﻧﺪروژنﻫﺎ و ﻛﻮرﺗﻴﺰول ﺑﻪ ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ و
اﺛﺒﺎت رﺳﻴﺪه اﺳﺖ و از ﻃﺮﻓﻲ ﺑﻨﺎﺑﺮ ﺗﺤﻘﻴﻘـﺎت ﻣﺘﻌـﺪد ﻣﻤﻜـﻦ اﺳـﺖ
اﺳﺘﻘﺎﻣﺘﻲ در زﻧﺎن ﻣﺴﻦ ﭘﺎﻳﻴﻦﺗﺮ از زﻧﺎن ﺟﻮان ﺑﺎﺷـﺪ 5.در ﺗﺤﻘﻴﻘـﻲ ﻛـﻪ
ﻛﺎﻫﺶ ﺳﻄﻮح آﻧﺪروژنﻫﺎ در زﻧﺎن ﻣﺴﻦ ﺑﺎ ﻣﺸﻜﻼت ﺟﺴﻤﻲ و رواﻧـﻲ
Hakkinenروي 10زن ﻣﺴﻦ 67ﺳﺎﻟﻪ اﻧﺠـﺎم داد ،ﻧﺘﻴﺠـﻪ ﮔﺮﻓـﺖ ﻛـﻪ
ﻣﺨﺘﻠﻔﻲ ﺗﻮام ﺑﺎﺷﺪ 1.ﺑﺮرﺳﻲ راﻫﺒﺮدﻫﺎي ﺗﻤﺮﻳﻨﻲ ﮔﻮﻧﺎﮔﻮن در اﻳﻦ راﺑﻄﻪ
ﺳﻄﻮح ﺗﺴﺘﻮﺳﺘﺮون ﻣﺘﻌﺎﻗﺐ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﺷﺪﻳﺪ اﻓـﺰاﻳﺶ
ﺑﻪ ﻋﻨﻮان ﻳـﻚ روش ﻏﻴـﺮ داروﻳـﻲ ﺑـﺪون ﻋـﻮارض ﺟـﺎﻧﺒﻲ ﻣﻬـﻢ ﺑـﻪ
ﻣﻌﻨﻲداري ﻧﺪاﺷﺖ ،اﻣﺎ ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت ﺧﻮن ﺑﻌﺪ از ﻳﻚ ﺟﻠـﺴﻪ ﺗﻤـﺮﻳﻦ
ﻧﻈﺮ ﻣﻲرﺳﺪ .ﻟﺬا ﺿﺮورت و اﻫﻤﻴﺖ اﻧﺠﺎم اﻳﻦ ﭘﮋوﻫﺶ را ﻣﻲﺗـﻮان ﺑـﺎ
Copeland
ﺑﻴﺎن اﻳﻦ ﺳﻮال ﺗﺤﻘﻴﻘﻲ ﻣﻄﺮح ﻛﺮد ﻛﻪ آﻳﺎ ﻣﺪاﺧﻠﻪ ﻳـﻚ ﺟﻠـﺴﻪ ﺗﻤـﺮﻳﻦ
روي 30زن ﺳﺎﻟﻢ در ﭘﻨﺞ ﮔﺮوه ﺳﻨﻲ ﻣﺘﻔﺎوت 16ﺗﺎ 69ﺳﺎل اﻧﺠﺎم داد،
ﻣﻘــﺎوﻣﺘﻲ و ﻳــﻚ ﺟﻠــﺴﻪ ﺗﻤــﺮﻳﻦ اﺳــﺘﻘﺎﻣﺘﻲ ﻣﻨﺠــﺮ ﺑــﻪ ﺗﻐﻴﻴــﺮات
ﺑﻪ اﻳﻦ ﻧﺘﻴﺠﻪ رﺳـﻴﺪ ﻛـﻪ ﭘـﺲ از ﻣﺪاﺧﻠـﻪ ﻫـﺮ دو ﺗﻤـﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ و
ﺣﺎد آﻧﺪروژنﻫـﺎ ،ﻛـﻮرﺗﻴﺰول و ﻻﻛﺘـﺎت زﻧـﺎن ﺳـﻨﻴﻦ 50ﺗـﺎ 60ﺳـﺎﻟﻪ
ﻣﻘﺎوﻣﺘﻲ ﻳﻚ ﺟﻠﺴﻪاي ﺳﻄﻮح ﻫﻮرﻣﻮن ﺗﺴﺘﻮﺳﺘﺮون در ﺗﻤﺎم ﮔﺮوهﻫـﺎي
ﻣﻲﺷﻮد ﻳﺎ ﺧﻴﺮ؟
ﻣﻘﺎوﻣﺘﻲ ﺷﺪﻳﺪ اﻓﺰاﻳﺶ ﻣﻌﻨـﻲدار ﻳﺎﻓـﺖ 24.در ﺗﺤﻘﻴﻘـﻲ ﻛـﻪ
18
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
112
ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻨﺎت ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﺑﺮ آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن
ﺗﺮﺗﻴﺐ در ﺟﻠﺴﺎت ﺗﻤﺮﻳﻦ اﺳﺘﻘﺎﻣﺘﻲ ،ﻣﻘﺎوﻣﺘﻲ و اﺳـﺘﺮاﺣﺖ و ﺑـﻪ ﻃـﻮر
روش ﺑﺮرﺳﻲ
ﻫﻢزﻣﺎن و ﻣﻮازي ﮔﺮوه دوم ﺑﻪ ﺗﺮﺗﻴﺐ در ﺟﻠـﺴﺎت ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ، اﻳــﻦ ﺗﺤﻘﻴـــﻖ از ﻧــﻮع ﻧﻴﻤــﻪ ﺗﺠـــﺮﺑﻲ ﺑــﺎ ﻃــﺮح ﭘــﻴﺶآزﻣـــﻮن و
اﺳﺘﻘﺎﻣﺘﻲ و اﺳﺘﺮاﺣﺖ ﺷﺮﻛﺖ ﻛﺮدﻧﺪ .ﺑﻨﺎﺑﺮاﻳﻦ ﺗﻤﺎﻣﻲ آزﻣـﻮدﻧﻲﻫـﺎ ﻃـﻲ
ﭘﺲآزﻣﻮن ،ﺑﺎ ﻳﻚ ﮔﺮوه آزﻣﻮدﻧﻲ )ﺟﺎﺑﻪﺟﺎﻳﻲ -ﻣﺘﻘﺎﻃﻊ( ﺑﻮد ﻛﻪ در ﺳﺎل
12روز در ﺳﻪ ﺟﻠﺴﻪ ﻣﺨﺘﻠـﻒ )ﻳـﻚ ﺟﻠـﺴﻪ ﺗﻤـﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ ،ﻳـﻚ
1389 -90در ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي ورزﺷﻲ داﻧﺸﮕﺎه ﻓﺮدوﺳﻲ ﻣﺸﻬﺪ اﻧﺠﺎم
ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و ﻳﻚ ﺟﻠﺴﻪ اﺳـﺘﺮاﺣﺖ ﻳـﺎ ﻛﻨﺘـﺮل( ﺑـﺎ ﻓﺎﺻـﻠﻪ
ﺷــﺪ .ﻧﻤﻮﻧــﻪ آﻣــﺎري ﺗﺤﻘﻴــﻖ ﺷــﺎﻣﻞ 10زن ﻣــﺴﻦ )ﻣﻴــﺎﻧﮕﻴﻦ ﺳــﻦ:
ﭼﻬﺎر روز اﺳﺘﺮاﺣﺖ ﺑﻴﻦ ﺟﻠﺴﺎت ﻗـﺮار ﻣـﻲﮔﺮﻓﺘﻨـﺪ .ﺗﻤـﺎﻣﻲ ﺟﻠـﺴﺎت
54/30±3/74ﺳﺎل ،ﻧﻤﺎﻳﻪ ﺗﻮده ﺑﺪن 24/88±2/07 :ﻛﻴﻠﻮﮔﺮم ﺑﺮ ﻣﺘﺮﻣﺮﺑﻊ
)ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و اﺳﺘﺮاﺣﺖ( ﺑﻴﻦ ﺳﺎﻋﺖ 8ﺗﺎ 10:30ﺻـﺒﺢ اﻧﺠـﺎم
و درﺻﺪ ﭼﺮﺑﻲ ﺑﺪن ﻛﻢﺗﺮ از (%36ﻏﻴﺮ ﻓﻌﺎل ﺳﺎﻛﻦ ﺷﻬﺮ ﻣﺸﻬﺪ ﺑﻮدﻧـﺪ
ﺷﺪ .ﺑﻪ آزﻣﻮدﻧﻲﻫﺎ ﮔﻔﺘﻪ ﺷﺪ 24ﺳﺎﻋﺖ ﻗﺒـﻞ از ﻫـﺮ ﻛـﺪام از ﺟﻠـﺴﺎت
ﻛﻪ ﺑﻪ ﺷﻴﻮه ﻫﺪفدار و در دﺳﺘﺮس از ﻣﻴـﺎن 46زن داوﻃﻠـﺐ اﻧﺘﺨـﺎب
ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و اﺳﺘﺮاﺣﺖ از ﻓﻌﺎﻟﻴﺖ ﺑﺪﻧﻲ ﺷﺪﻳﺪ اﺟﺘﻨـﺎب
ﺷﺪﻧﺪ .ﭘﻴﺶ از اﻧﺘﺨﺎب ﻧﻤﻮﻧﻪ آﻣﺎري ،اﻃﻼﻋﺎت ﻓﺮدي ،ﺳﺎﺑﻘﻪ ورزﺷﻲ و
ﻛﻨﻨﺪ ،رژﻳﻢ ﻏﺬاﻳﻲ ﺛﺎﺑﺘﻲ داﺷﺘﻪ ﺑﺎﺷﻨﺪ و دو ﺳﺎﻋﺖ ﻗﺒـﻞ از ﻫـﺮ ﺟﻠـﺴﻪ
ﭘﺰﺷﻜﻲ 46زن داوﻃﻠﺐ ﻣـﺸﺎرﻛﺖ در ﺗﺤﻘﻴـﻖ از ﻃﺮﻳـﻖ ﭘﺮﺳـﺶﻧﺎﻣـﻪ
ﻛﺎﻓﻴﻴﻦ ﻣﺼﺮف ﻧﻜﻨﻨﺪ .ﺻﺒﺢ روز ﻫﺮ ﺟﻠﺴﻪ ) 2/5ﺳﺎﻋﺖ ﻗﺒﻞ از ﺷـﺮوع
ﺟﻤﻊآوري ﺷﺪ .در اﻳﻦ ﺗﺤﻘﻴﻖ ﻣﻼك ورود ﺑﻪ ﻣﻄﺎﻟﻌﻪ ،ﺳﻦ ﺣـﺪاﻗﻞ 50
ﺟﻠﺴﻪ( ﺑﻪ ﺗﻤﺎم آزﻣﻮدﻧﻲﻫﺎ ﻳﻚ وﻋـﺪه ﻏـﺬاي اﺳـﺘﺎﻧﺪارد ﻣﻌــﺎدل 4/3
و ﺣﺪاﻛﺜﺮ 60ﺳﺎل و ﮔﺬﺷﺖ ﺣﺪاﻗﻞ ﻳﻚ ﺳﺎل از ﺳﻦ ﻳﺎﺋﺴﮕﻲ در ﻧﻈـﺮ
ﻛﻴﻠـﻮﻛﺎﻟﺮي اﻧــﺮژي ﺑـﻪ ازاي ﻫـﺮ ﻛــﻴﻠﻮﮔﺮم وزن ﺑـﺪن ،ﺷــﺎﻣﻞ %65
ﮔﺮﻓﺘﻪ ﺷﺪه ﺑﻮد .ﺑﺮاي ﻛﻨﺘﺮل ﺑﻬﺘﺮ ﻋﻮاﻣﻞ ﻣﺪاﺧﻠـﻪﻛﻨﻨـﺪه ،اﻓـﺮاد ﭼـﺎق و
ﻛﺮﺑﻮﻫﻴﺪرات %20 ،ﭼﺮﺑﻲ و %15ﭘﺮوﺗﻴﻴﻦ داده ﺷﺪ 27.در اﻳﻦ ﭘـﮋوﻫﺶ
ﻛﺴﺎﻧﻲ ﻛﻪ ﺳﺎﺑﻘﻪ ﺑﻴﻤﺎري ،ﻳﺎﺋﺴﮕﻲ ﻏﻴﺮﻃﺒﻴﻌـﻲ ،ﻣـﺼﺮف دارو و ﻣﻜﻤـﻞ
از ﻧﺎن ﺗﺴﺖ ﻣﺎرك ﺳﻪ ﻧﺎن و ﭘﻨﻴﺮ ﺧﺎﻣﻪاي ﻣﺎرك ﭘﮕﺎه اﺳﺘﻔﺎده ﺷـﺪ ﻛـﻪ
اﺳﺘﺮوﻳﻴﺪي ،ﺳﺎﺑﻘﻪ ورزﺷﻲ و ﻣﺼﺮف دﺧﺎﻧﻴﺎت داﺷﺘﻨﺪ از ﺗﺤﻘﻴـﻖ ﻛﻨـﺎر
ﻫﺮ دو ﻣﺤﺼﻮل داراي ﻧﺸﺎن اﺳﺘﺎﻧﺪارد ﺑﻮدﻧﺪ .در اﻳﻦ ﺗﺤﻘﻴﻖ ﻳﻚ ﺟﻠﺴﻪ
ﮔﺬاﺷﺘﻪ ﺷﺪﻧﺪ .ﭘﺲ از ﮔﺰﻳﻨﺶ ﻧﻤﻮﻧﻪ آﻣﺎري ﻫﻤﻪ آزﻣﻮدﻧﻲﻫـﺎ در ﻣـﻮرد
ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﺑﻪ ﻣﺪت 45دﻗﻴﻘﻪ و ﺷﺎﻣﻞ ﺳـﻪ ﺳـﺖ 10ﺗﻜـﺮاري ﺑـﺎ
ﻣﺮاﺣﻞ ﺗﺤﻘﻴﻖ ﺗﻮﺟﻴﻪ ﺷـﺪﻧﺪ و ﺳـﭙﺲ ﻓـﺮم رﺿـﺎﻳﺖﻧﺎﻣـﻪ ﺷـﺮﻛﺖ در
%80ﻳﻚ ﺗﻜﺮار ﺑﻴﺸﻴﻨﻪ و ﺑﺎ اﺳﺘﺮاﺣﺖﻫﺎي ﻳﻚ دﻗﻴﻘـﻪاي ﺑـﻴﻦ ﺳـﺖﻫـﺎ
ﭘﮋوﻫﺶ و ﭘﺮﺳﺶﻧﺎﻣﻪﻫﺎى آﻣﺎدﮔﻲ اﻧﺠـﺎم ﻓﻌﺎﻟﻴـﺖ ورزﺷـﻲ )،(PAR-Q
روي دﺳﺘﮕﺎهﻫﺎي ﺑﺪنﺳﺎزي اﻳﺰوﺗﻮﻧﻴﻚ اﻧﺠـﺎم ﺷـﺪ .ﺣﺮﻛـﺎت ﺷـﺎﻣﻞ:
ﺳﻼﻣﺖ ﻋﻤﻮﻣﻲ ) ،(GHQ28وﺿـﻌﻴﺖ ﺗﻐﺬﻳـﻪ و ﻣﻄﺎﻟﻌـﻪ ﺳـﻼﻣﺖ زﻧـﺎن
(1ﭘﺮس ﺳﻴﻨﻪ ﺧﻮاﺑﻴﺪه (2 ،ﻛﺸﺶ دوﻃﺮﻓـﻪ ﺑـﻪ ﭘـﺎﻳﻴﻦ (3 ،ﭘـﺮس ﭘـﺎي
ﻣﺎﺳﺎﭼﻮﺳﺖ ) (MWHSرا ﺗﻜﻤﻴﻞ ﻛﺮدﻧﺪ .ﻗﺒﻞ از ﺷـﺮوع ﺗﺤﻘﻴـﻖ ﻣﺠـﻮز
ﻧﺸﺴﺘﻪ (4 ،ﺧﻢ ﻛﺮدن آرﻧﺞ (5 ،ﺑﺎز ﻛﺮدن آرﻧـﺞ (6 ،ﺧـﻢ ﻛـﺮدن زاﻧـﻮ،
ﻛﻤﻴﺘﻪ اﺧﻼق درﻳﺎﻓﺖ ﺷﺪ و ﻋﺪم ﻣﺤـﺪودﻳﺖ اﻧﺠـﺎم ﻓﻌﺎﻟﻴـﺖ ورزﺷـﻲ
(7ﺑﺎز ﻛﺮدن زاﻧﻮ و (8ﭘﺮس ﺳﺮﺷﺎﻧﻪ ﺑﻮد .ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ
آزﻣﻮدﻧﻲﻫﺎ ﺑﻪ وﺳﻴﻠﻪ ﭘﺰﺷﻚ ﺗﺄﻳﻴﺪ ﺷﺪ .ﻗﺪ و وزن اﻓﺮاد ﺑـﺪون ﻛﻔـﺶ و
ﺷﺎﻣﻞ 45دﻗﻴﻘﻪ ﻓﻌﺎﻟﻴﺖ روي دوﭼﺮﺧﻪ ﻛﺎرﺳﻨﺞ Technogymﺳـﺎﺧﺖ
ﺑﺎ ﻟﺒﺎسﻫﺎي ﺳﺒﻚ ﺗﻮﺳﻂ ﺑﺎﺳﻜﻮل ﺑﺎ دﻗﺖ 0/1ﻛﻴﻠﻮﮔﺮم و ﻧﻤﺎﻳـﻪ ﺗـﻮده
ﻛﺸﻮر اﻳﺘﺎﻟﻴﺎ ﺑﺎ ﺷﺪت 60ﺗﺎ 70درﺻﺪ ﺣﺪاﻛﺜﺮ اﻛـﺴﻴﮋن ﻣـﺼﺮﻓﻲ ﺑـﻮد.
ﺑﺪن و درﺻﺪ ﭼﺮﺑﻲ ﺑﺪن آزﻣﻮدﻧﻲﻫﺎ ﺑﻪ روش ﺑﻴﻮاﻟﻜﺘﺮﻳﻜﺎل اﻳﻤﭙـﺪاﻧﺲ
ﺷﺪت ﺗﻤﺮﻳﻦ ﺑﻪ ﻃﻮر ﻣﺪاوم ﺑﺎ اﺳﺘﻔﺎده از ﺿﺮﺑﺎن ﺳﻨﺞ ﭘﻼر ﻛﻨﺘﺮل ﺷـﺪ
(Inbody-720 Body
و آزﻣﻮدﻧﻲﻫﺎ ﻫﺮ ﭘﻨﺞ دﻗﻴﻘﻪ ﺑﺎ اﺳﺘﻔﺎده از ﺷـﺎﺧﺺ درك ﺗـﻼش ﺑـﻮرگ
) Composition Analyzerﺳﺎﺧﺖ ﻛﺸﻮر ﻛﺮه ﺟﻨﻮﺑﻲ اﻧﺪازهﮔﻴﺮي ﺷـﺪ.
) (Borgﺷﺪت ﺗﻤﺮﻳﻦ را اﻋﻼم ﻣﻲﻛﺮدﻧـﺪ .آزﻣـﻮدﻧﻲﻫـﺎ ﻗﺒـﻞ از ﺷـﺮوع
ﻫﺸﺖ و 12روز ﭘﻴﺶ از اوﻟﻴﻦ ﺟﻠﺴﻪ )ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﻳﺎ اﺳـﺘﻘﺎﻣﺘﻲ و
ﺗﻤﺮﻳﻨﺎت ﺑﻪ ﻣﺪت 10دﻗﻴﻘﻪ ﺑﺪن ﺧﻮد را ﮔﺮم ﻣﻲﻛﺮدﻧﺪ .در اﻳﻦ ﺗﺤﻘﻴﻖ
ﻳﺎ اﺳﺘﺮاﺣﺖ( ،ﺑﻪ ﺗﺮﺗﻴﺐ ﺣﺪاﻛﺜﺮ اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ آزﻣﻮدﻧﻲﻫﺎ ﺑﺎ اﺳﺘﻔﺎده
ﻃــﻲ اﺳــﺘﺮاﺣﺖ )ﻛﻨﺘــﺮل( ﺑــﻪ ﻣــﺪت 45دﻗﻴﻘــﻪ ﻫــﻴﭻ ﻓﻌــﺎﻟﻴﺘﻲ اﻧﺠــﺎم
ﺗﻮﺳـــﻂ دﺳـــﺘﮕﺎه ﺳـــﻨﺠﺶ ﺗﺮﻛﻴـــﺐ ﺑـــﺪﻧﻲ
5
از آزﻣﻮن آﻣﺎدﮔﻲ ﻫﻮازي دوﭼﺮﺧﻪ آﺳﺘﺮاﻧﺪ و ﻫﻢﭼﻨـﻴﻦ آزﻣـﺎﻳﺶ ﻳـﻚ
ﻧﻤﻲﮔﺮﻓﺖ و اﻓﺮاد ﻣﻲﻧﺸﺴﺘﻨﺪ .ﻧﻤﻮﻧﻪﮔﻴﺮي ﺧﻮﻧﻲ در ﺳﻪ ﻣﺮﺣﻠﻪ ﭘﻴﺶ،
ﺗﻜﺮار ﺑﻴﺸﻴﻨﻪ ﺣﺮﻛﺎت وزﻧﻪ ﺗﻤﺮﻳﻨﻲ ﺗﻌﻴﻴﻦ ﺷﺪ .دادهﻫﺎي ﻣﺮﺑﻮط ﺑﻪ ﺳﻦ،
ﺑﻼﻓﺎﺻﻠﻪ و 15دﻗﻴﻘﻪ ﺑﻌﺪ از اﺗﻤﺎم ﻫﺮ ﺟﻠﺴﻪ )ﻣﻘﺎوﻣﺘﻲ ﻳﺎ اﺳﺘﻘﺎﻣﺘﻲ و ﻳﺎ
ﺷﺎﺧﺺﻫﺎي اﺑﻌﺎد ﺑﺪﻧﻲ و اوج اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ آزﻣﻮدﻧﻲﻫﺎ در ﺟـﺪول
اﺳﺘﺮاﺣﺖ( اﻧﺠﺎم ﺷـﺪ .در ﻫـﺮ ﻧﻮﺑـﺖ ﭘـﻨﺞ ﻣﻴﻠـﻲﻟﻴﺘـﺮ ﺧـﻮن از ورﻳـﺪ
1آﻣﺪه اﺳﺖ .در ﻃﺮح ﺗﺤﻘﻴﻖ ﻣﺘﻘﺎﻃﻊ ﻧﺨﺴﺖ ﻧﻤﻮﻧﻪﻫﺎي آﻣﺎري ﺑﻪ ﻃﻮر
آﻧﺘﻪﻛﻮﺑﻴﺘﺎل ﮔﺮﻓﺘﻪ ﺷﺪ .ﻧﻤﻮﻧﻪﻫﺎي ﺧـﻮﻧﻲ ﺑﻌـﺪ از ﺟﺪاﺳـﺎزي ﺳـﺮم ،در
ﺗﺼﺎدﻓﻲ ﺑﻪ دو ﮔﺮوه ﭘﻨﺞ ﻧﻔﺮي ﺗﻘـﺴﻴﻢ ﺷـﺪﻧﺪ و ﺳـﭙﺲ ﮔـﺮوه اول ﺑـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
دﻣﺎي
C
º
-18ﻓﺮﻳﺰ ﺷﺪه و ﭘﺲ از ﺟﻤﻊآوري ،ﺗﻤﺎﻣﻲ ﻧﻤﻮﻧﻪﻫﺎ در ﻳـﻚ
دﻧﻴﺎ ﺻﻮرﺗﻲ ﺟﺎﺑﻠﻮ و ﻫﻤﻜﺎران
113
روز ﻣــﻮرد ﺑﺮرﺳــﻲ ﻗــﺮار ﮔﺮﻓﺘﻨــﺪ .ﻣﻘــﺎدﻳﺮ ﺗــﺴﺘﻮﺳﺘﺮون ،دﻫﻴــﺪرواﭘﻲ
ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ در ﺟﺪول 2ﻧـﺸﺎن داده ﺷـﺪه اﺳـﺖ .ﻫﻤـﺎنﻃـﻮر ﻛـﻪ
آﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت و ﻛﻮﺗﻴﺰول ﺑـﺎ روش Chemiluminescenceو ﺑـﺎ
ﻣﺸﺎﻫﺪه ﻣﻲﺷﻮد ﻋﻠـﻲرﻏـﻢ اﻳـﻦ ﻛـﻪ ﺗﻐﻴﻴـﺮات درون ﮔﺮوﻫـﻲ ﻣﻘـﺎدﻳﺮ
دﺳﺘﮕﺎه و ﻛﻴﺖ Liaisonﺳﺎﺧﺖ ﻛﺸﻮر اﻧﮕﻠﺴﺘﺎن اﻧـﺪازهﮔﻴـﺮي ﺷـﺪﻧﺪ.
ﺗﺴﺘﻮﺳﺘﺮون ﻫﺮ دو ﮔـﺮوه ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ و اﺳـﺘﻘﺎﻣﺘﻲ ﻃـﻲ ﻣﺮاﺣـﻞ
ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت ﻧﻴﺰ ﺑﺎ دﺳﺘﮕﺎه ﺑﻴﻮﺷﻴﻤﻲ Selectraو ﻛﻴﺖ ﺷﺮﻛﺖ ﭘـﺎرس
ﻣﺨﺘﻠﻒ ﻣﻌﻨﻲدار اﺳﺖ ) (P<0/05و اﻳـﻦ ﻣﻘـﺎدﻳﺮ ﺑﻼﻓﺎﺻـﻠﻪ و ﭘـﺲ از
آزﻣﻮن ﺳﺎﺧﺖ ﻛﺸﻮر اﻳﺮان ﻣﻮرد ارزﻳﺎﺑﻲ ﻗﺮار ﮔﺮﻓﺖ .دادهﻫﺎ ﺑﺎ اﺳﺘﻔﺎده
ﮔﺬﺷﺖ 15دﻗﻴﻘﻪ از ﻣﺪاﺧﻠﻪ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ و اﺳـﺘﻘﺎﻣﺘﻲ
از ﻧﺮماﻓﺰاري آﻣﺎري SPSSوﻳﺮاﺳﺖ 11/5ﺗﺠﺰﻳﻪ و ﺗﺤﻠﻴـﻞ ﺷـﺪﻧﺪ ﺑـﻪ
اﻓﺰاﻳﺶ داﺷﺘﻪ اﺳﺖ وﻟﻲ اﻳﻦ ﺗﻐﻴﻴﺮات ﺑﻪ اﻧـﺪازهاي ﻧﻴـﺴﺖ ﻛـﻪ ﺑﺘﻮاﻧـﺪ
Levene
روي ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﺗﺎﺛﻴﺮﮔﺬار ﺑﺎﺷﺪ .ﺑﻪ ﻋﺒﺎرت دﻳﮕـﺮ ،ﺗﻐﻴﻴـﺮات
ﻃﻮري ﻛﻪ از روش ﺗﺤﻠﻴﻞ اﻛﺘﺸﺎﻓﻲ Kolmogorov-smirnovو
ﺑﻪ ﺗﺮﺗﻴﺐ ﺑﺮاي ﺗﻌﻴﻴﻦ ﻧﺮﻣﺎل ﺑﻮدن ﺗﻮزﻳـﻊ دادهﻫـﺎ و ﺗﺠـﺎﻧﺲ وارﻳـﺎﻧﺲ ﮔﺮوهﻫﺎ و از آزﻣﻮن اﻧﺪازهﻫـﺎي ﺗﻜـﺮاري و ﺗﻌﻘﻴﺒـﻲ Bonferroniﺑـﺮاي ﺗﻌﻴﻴﻦ ﺗﻐﻴﻴﺮات درون و ﺑﻴﻦ ﮔﺮوﻫﻲ اﺳﺘﻔﺎده ﺷﺪ .ﺑﺮاي ﺗـﺼﻤﻴﻢ آﻣـﺎري
ﺟﺪول :1 -ﺷﺎﺧﺺﻫﺎي اﺑﻌﺎد ﺑﺪﻧﻲ و اوج اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ آزﻣﻮدﻧﻲﻫﺎ ﺷﺎﺧﺺﻫﺎ
ﻣﻴﺎﻧﮕﻴﻦ
اﻧﺤﺮافﻣﻌﻴﺎر
ﺳﻦ )ﺳﺎل(
54/30
3/74
ﻗﺪ )ﺳﺎﻧﺘﻲﻣﺘﺮ(
161/92
5/93
وزن )ﻛﻴﻠﻮﮔﺮم(
65/42
8/28
ﻧﻤﺎﻳﻪ ﺗﻮده ﺑﺪن )ﻛﻴﻠﻮﮔﺮم ﺑﺮ ﻣﺘﺮﻣﺮﺑﻊ(
24/88
2/07
درﺻﺪ ﭼﺮﺑﻲ ﺑﺪن )درﺻﺪي از وزن ﺑﺪن(
33/50
2/63
ﻣﻘﺎدﻳﺮ ﺗﺴﺘﻮﺳﺘﺮون ،دﻫﻴـﺪرواﭘـﻲآﻧﺪرﺳﺘـﺮون ﺳﻮﻟﻔـﺎت ،ﻛﻮرﺗﻴـﺰول و
ﺣﺪاﻛﺜﺮ اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ )ﻣﻴﻠﻲﻟﻴﺘﺮ /ﻛﻴﻠﻮﮔﺮم/
27/32
2/49
ﻻﻛﺘﺎت ﮔـﺮوه ﺗﻤﺮﻳـﻦ ﻣﻘﺎوﻣﺘـﻲ ،اﺳﺘﻘﺎﻣﺘـﻲ و اﺳﺘﺮاﺣـﺖ )ﻛﻨﺘﺮل( ﻃﻲ
دﻗﻴﻘﻪ(
ﺳﻄﺢ ﻣﻌﻨﻲداري P<0/05در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪ.
ﻳﺎﻓﺘﻪﻫﺎ ﻧﺘﺎﻳﺞ آزﻣﻮن ﺗﺤﻠﻴﻞ وارﻳـﺎﻧﺲ )اﻧـﺪازهﻫـﺎي ﺗﻜـﺮاري( ﻣﺮﺑـﻮط ﺑـﻪ
ﺟﺪول :2 -ﺗﻐﻴﻴﺮات درون و ﺑﻴﻦ ﮔﺮوﻫﻲ ﺗﺴﺘﻮﺳﺘﺮون ،دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت ﺳﺮم ﮔﺮوهﻫﺎ ﻣﺘﻐﻴﺮﻫﺎ
ﺟﻠﺴﻪﻫﺎ
ﮔﺮوه ﭘﻴﺶ از ﺗﻤﺮﻳﻦ
*
ﺗﻐﻴﻴﺮات درون ﮔﺮوﻫﻲ
ﺑﻼﻓﺎﺻﻠﻪ
15دﻗﻴﻘﻪ
ﭘﺲ از ﺗﻤﺮﻳﻦ
P
ﭘﺲ از ﺗﻤﺮﻳﻦ
ﻣﻘﺪار
ﺗﺴﺘﻮﺳﺘﺮون
ﻣﻘﺎوﻣﺘﻲ
0/19±0/13
0/28±0/07
0/32±0/12
6/386
†0/008
)ﻧﺎﻧﻮﮔﺮم ﺑﺮ ﻣﻴﻠﻲﻟﻴﺘﺮ(
اﺳﺘﻘﺎﻣﺘﻲ
0/18±0/10
0/30±0/08
0/32±0/16
8/311
†0/003
ﻛﻨﺘﺮل
0/22±0/14
0/24±0/13
0/27±0/14
1/077
0/362
دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت
ﻣﻘﺎوﻣﺘﻲ
49/29±41/21
55/99±39/35
58/94±43/27
3/816
†
)ﻣﻴﻜﺮوﮔﺮم ﺑﺮ دﺳﻲﻟﻴﺘﺮ(
اﺳﺘﻘﺎﻣﺘﻲ
45/41±34/48
48/37±31/05
54/20±46/74
1/476
0/255
ﻛﻨﺘﺮل
45/51±33/97
45/50±36/99
47/42±41/67
0/186
0/832
ﻛﻮرﺗﻴﺰول
ﻣﻘﺎوﻣﺘﻲ
6/40±1/64
5/10±1/06
5/32±1/21
3/407
0/083
)ﻣﻴﻜﺮوﮔﺮم ﺑﺮ دﺳﻲﻟﻴﺘﺮ(
اﺳﺘﻘﺎﻣﺘﻲ
6/26±1/64
8/78±3/31
7/87±2/86
3/059
0/101
F
0/042
ﻛﻨﺘﺮل
5/83±1/88
5/25±1/79
5/52±0/90
0/444
0/648
ﻻﻛﺘﺎت
ﻣﻘﺎوﻣﺘﻲ
26/60±4/79
40/00±7/40
27/40±4/67
17/671
†0/000
)ﻣﻴﻜﺮوﮔﺮم ﺑﺮ دﺳﻲﻟﻴﺘﺮ(
اﺳﺘﻘﺎﻣﺘﻲ
24/30±4/35
34/40±8/34
26/70±3/89
13/504
†
ﻛﻨﺘﺮل
25/70±4/83
30/10±5/88
29/40±5/78
8/279
ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺪار
P
F
0/111
0/129
7/677
1/435
0/895
0/880
†
0/002
0/256
0/000
†0/003
* اﻋﺪاد ﺑﻪ ﺻﻮرت ﻣﻴﺎﻧﮕﻴﻦ ±اﻧﺤﺮافﻣﻌﻴﺎر ﺑﻴﺎن ﺷﺪهاﻧﺪ P<0/05 † .ﻣﻌﻨﻲدار در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪه اﺳﺖ.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻨﺎت ﻣﻘﺎوﻣﺘﻲ و اﺳﺘﻘﺎﻣﺘﻲ ﺑﺮ آﻧﺪروژنﻫﺎ ،ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن
114
ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﺗﺴﺘﻮﺳﺘﺮون ﻫﺮ ﺳﻪ ﮔﺮوه ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ،
ﺗﺴﺘﻮﺳﺘﺮون ﻣﺘﻌﺎﻗﺐ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ و اﺳـﺘﻘﺎﻣﺘﻲ 5را ﮔـﺰارش ﻛـﺮده و 25و24
ﻫﻢ اﻳﻦ ﻃﻮر در ﺧـﺼﻮص
اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل ﻣﻌﻨﻲدار ﻧﻴﺴﺖ .ﻗﺎﺑﻞ ذﻛﺮ اﻳﻦ ﻛﻪ ﺗﻐﻴﻴﺮات ﻣﻘﺎدﻳﺮ
ﺑﻌﻀﻲ ﻫﻴﭻﮔﻮﻧﻪ ﺗﻐﻴﻴﺮي را ﻧﺸﺎن ﻧﺪاﻧﺪ.
ﺗﺴﺘﻮﺳﺘﺮون ﻣﺮﺑﻮط ﺑﻪ ﻫﺮ ﺳﻪ ﮔﺮوه ﻃﻲ ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ از ﻳﻚ اﻟﮕﻮي
ﭘﺎﺳﺦ DHEASﺑﻪ ﺗﻤﺮﻳﻦ ورزﺷـﻲ و ﻓﻌﺎﻟﻴـﺖ ﺑـﺪﻧﻲ ،ﺑﺮﺧـﻲ ﻣﻄﺎﻟﻌـﺎت
ﻃﻲ
اﻓﺰاﻳﺶ ﻣﻌﻨﻲدار DHEASﺑﻪ ﺗﻤﺮﻳﻦ اﺳﺘﻘﺎﻣﺘﻲ را ﮔﺰارش ﻛﺮدهاﻧـﺪ 26.در
ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ ﻧﺸﺎن ﻣﻲدﻫﺪ ﻛﻪ از ﻣﻴﺎن اﺛﺮ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ
ﺗﺤﻘﻴﻖ ﻣﺎ ﻣﻘﺎدﻳﺮ درون ﮔﺮوﻫﻲ ﺗﺴﺘﻮﺳﺘﺮون ﺑﻌﺪ از ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ و
و اﺳﺘﻘﺎﻣﺘﻲ ﺗﻨﻬﺎ ﻣﺪاﺧﻠﻪ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ اﺳﺖ ﻛﻪ ﺑﺮ ﭘﺎﺳﺦ
اﺳﺘﻘﺎﻣﺘﻲ ﺗﻐﻴﻴﺮ ﻣﻌﻨﻲداري ﻳﺎﻓﺖ ﻛﻪ ﺑﺎ ﻧﺘﺎﻳﺞ و ﻫﻤﻜﺎران ﻫﻢﺧﻮاﻧﻲ دارد
ﻣﺸﺎﺑﻪ ﭘﻴﺮوي ﻣﻲﻛﻨﺪ .ﺗﻐﻴﻴﺮات درون ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ
ﺣﺎد
DHEAS
DHEAS
ﺗﺎﺛﻴﺮ ﻣﻌﻨﻲدار داﺷﺘﻪ اﺳﺖ ) .(P<0/05ﺿﻤﻦ اﻳﻦ ﻛﻪ
25و24و5
و ﺑﺎ ﻧﺘﺎﻳﺞ Hakkinenﻣﻐﺎﻳﺮ اﺳﺖ.
ﻫﻢﭼﻨﻴﻦ ﻣﻘﺎدﻳﺮ درون ﮔﺮوﻫﻲ
ﻣﺮﺑﻮط ﺑﻪ ﻫﺮ ﺳﻪ ﮔﺮوه ﻃﻲ ﻣﺮاﺣﻞ
DHEASﺳﺮم ﺗﻨﻬﺎ ﺑﻌﺪ از ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﺗﻐﻴﻴﺮ ﻣﻌﻨـﻲداري ﻳﺎﻓـﺖ ﻛـﻪ
ﻣﺨﺘﻠﻒ از ﻳﻚ اﻟﮕﻮي ﻣﺸﺎﺑﻪ ﭘﻴﺮوي ﻣﻲﻛﻨﺪ ،ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ
ﻣﻮاﻓـﻖ ﺑــﺎ ﻧﺘـﺎﻳﺞ ﺗﺤﻘﻴــﻖ Johnsonﻣـﻲﺑﺎﺷــﺪ 26.در واﻗـﻊ ﭘﺎﺳــﺦﻫــﺎي
ﻣﻴﺎﻧﮕﻴﻦ ﺗﻐﻴﻴﺮات ﻣﻘﺎدﻳﺮ ﻣﻘﺎدﻳﺮ
DHEAS
DHEAS
ﻫﺮ ﺳﻪ ﮔﺮوه ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل
ﻣﻌﻨﻲدار ﻧﻴﺴﺖ .در ﺣﺎﻟﻲ ﻛﻪ ﺗﻐﻴﻴﺮات درون ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﻣﺮﺑﻮط ﺑﻪ ﻫﺮ ﺳﻪ ﮔﺮوه ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل ﻃﻲ ﻣﺮاﺣﻞ
28
ﻫﻮرﻣﻮﻧﻲ ﺑﻪ ﺗﻤﺮﻳﻦ ﺑﻪ ﻋﻮاﻣﻠﻲ ﭼـﻮن ﻣـﺪت و ﻧـﻮع ﺗﻤـﺮﻳﻦ ،ﺷـﺪت 29
ﻓﻌﺎﻟﻴﺖ ﻋـﻀﻼﻧﻲ ،زﻣﻴﻨـﻪ ژﻧﺘﻴﻜـﻲ ،ﺟﻨـﺴﻴﺖ ،ﺗﻐﺬﻳـﻪ ،ﺳـﻦ ،ﭼﺮﺧـﻪ 28
30
ﺷﺒﺎﻧﻪروزي و ﻣﻴـﺰان ورزﻳﺪﮔﻲ اﻓـﺮاد ﺑـﺴﺘﮕﻲ دارد .ﻣﻴــﺰان ﺗـﻮده 31-33
34-38
ﺷـﺪت و ﺣﺠـﻢ ﺗﻤـﺮﻳﻦ،
ﻣﻴـﺰان
ﻣﺨﺘﻠﻒ ﻣﻌﻨﻲدار ﻧﻴﺴﺖ .ﻣﻴﺎﻧﮕﻴﻦ ﺗﻐﻴﻴﺮات ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﻣﺮﺑﻮط ﺑﻪ
ﻋﻀﻼﻧﻲ درﮔﻴﺮ در ﻓﻌﺎﻟﻴﺖ،
ﻫﺮ ﺳﻪ ﮔﺮوه ﻃﻲ ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ از ﻳﻚ اﻟﮕﻮي ﻣﺸﺎﺑﻪ ﭘﻴﺮوي ﻧﻤﻲﻛﻨﺪ،
اﺳﺘﺮاﺣﺖ ﺑﻴﻦ ﺳﺖﻫﺎ 34،ﻏﺬاي ﻣﺼﺮﻓﻲ 39،ﺳﻦ 40و ﺗﺠﺮﺑﻪ ﺗﻤﺮﻳﻨـﻲ
ﺑﻪ ﻃﻮري ﻛﻪ ﺗﻨﻬﺎ در ﻧﺘﻴﺠﻪ ﻣﺪاﺧﻠﻪ ﺗﻤﺮﻳﻦ اﺳﺘﻘﺎﻣﺘﻲ اﺳﺖ ﻛﻪ ﻣﻘﺎدﻳﺮ
ﻣﺴﺘﻘﻞ از ﻣﻴﺰان ﻗـﺪرت ﻋـﻀﻼﻧﻲ از ﻋﻮاﻣـﻞ ﻣـﺆﺛﺮ ﺑـﺮ ﻣﻴــﺰان ﭘﺎﺳـﺦ
42و41
42
ﻛﻮرﺗﻴﺰول اﻓﺰاﻳﺶ ﻣﻲﻳﺎﺑﺪ .ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﻫﺮ
ﻫﻮرﻣـﻮن ﺗﺴﺘﻮﺳﺘﺮون ﻫـﺴﺘﻨﺪ .ﻧـﺸﺎن داده ﺷـﺪه ﻛـﻪ ﭘﺮوﺗﻜـﻞﻫـﺎي
ﺳﻪ ﮔﺮوه ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل ﻃﻲ ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ
ﺗﻤﺮﻳﻨــﻲ ﺷــﺪﻳﺪ ﻛــﻪ ﻋــﻀﻼت ﺑــﺰرگ و ﻧﻴــﺰ ﭼﻨــﺪ ﻣﻔــﺼﻞ را درﮔﻴــﺮ
ﻣﻌﻨﻲدار اﺳﺖ ) .(P<0/05ﺑﺮاﺳﺎس ﻧﺘﺎﻳﺞ آزﻣﻮن ﺗﻌﻘﻴﺒﻲ ﺑﻨﻔﺮوﻧﻲ ﺑﻴﻦ
43
ﻣﻲﺳﺎزﻧﺪ ،ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﺣﺎد ﻏﻠﻈﺖﻫـﺎي ﺗـﺴﺘﻮﺳﺘﺮون ﻣـﻲﺷـﻮﻧﺪ.
ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﮔﺮوه ﺗﻤﺮﻳﻦ اﺳﺘﻘﺎﻣﺘﻲ ﺑﺎ ﻛﻨﺘﺮل و اﺳﺘﻘﺎﻣﺘﻲ ﺑﺎ
ﺣﺮﻛﺎﺗﻲ ﻣﺎﻧﻨﺪ ﻟﻴﻔﺖ اﻟﻤﭙﻴﻚ 44،ﻟﻴﻔﺖ ﻣﺮده 45و اﺳﻜﺎت ﭘﺮﺷﻲ 32ﻛﻪ ﺗﻮده
ﻣﻘﺎوﻣﺘﻲ ﺗﻔﺎوت ﻣﻌﻨﻲدار اﺳﺖ ) .(P<0/05ﻫﻢﭼﻨﻴﻦ ﻧﺘﺎﻳﺞ آزﻣﻮن
ﻋﻀﻼﻧﻲ ﺑﺰرﮔﻲ را درﮔﻴﺮ ﻓﻌﺎﻟﻴﺖ ﻣﻲﻛﻨﻨﺪ ﻧﺴﺒﺖ ﺑﻪ ﺣﺮﻛﺎﺗﻲ ﻛـﻪ ﺗـﻮده
ﺗﺤﻠﻴﻞ وارﻳﺎﻧﺲ )اﻧﺪازهﻫﺎي ﺗﻜﺮاري( ﻣﺮﺑﻮط ﺑﻪ ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت ﮔﺮوه
ﻋﻀﻼﻧﻲ ﻛﻮﭼﻚ را درﮔﻴﺮ ﻣﻲﺳﺎزﻧﺪ ﺑﻪ ﺳـﺒﺐ ﻧـﺮخ ﻣﺘـﺎﺑﻮﻟﻴﻜﻲ ﺑـﺎﻻﺗﺮ
ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ،اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل ﻃﻲ ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ ﻧﺸﺎن ﻣﻲدﻫﺪ
ﺑﺎﻋﺚ اﻓﺰاﻳﺶ ﺗﺤﺮﻳﻚ ﺗﺮﺷﺢ ﺗـﺴﺘﻮﺳﺘﺮون ﻣـﻲﺷـﻮﻧﺪ47.و 46ﻧـﺸﺎن داده
ﻛﻪ ﺗﻐﻴﻴﺮات درون ﮔﺮوﻫﻲ ﻻﻛﺘﺎت ﻫﺮ ﺳﻪ ﮔﺮوه ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ،
ﺷﺪه زﻣﺎﻧﻲ ﻛﻪ ﻣﻴﺰان ﺑﺎر در ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ از 10ﺗﻜﺮار ﺑﻴﺸﻴﻨﻪ ﺑـﻪ 10
اﺳﺘﻘﺎﻣﺘﻲ و ﻛﻨﺘﺮل ﻣﻌﻨﻲدار اﺳﺖ ) .(P<0/05در ﺻﻮرﺗﻲ ﻛﻪ ﺗﻐﻴﻴﺮات
ﺗﻜﺮار ﺑﺎ %70ﻳﻚ ﺗﻜﺮار ﺑﻴﺸﻴﻨﻪ ﻛﺎﻫﺶ ﻳﺎﺑﺪ ،ﭘﺎﺳﺦﻫﺎي ﻫﻮرﻣـﻮﻧﻲ ﻫـﻢ
ﺑﻴﻦ ﮔﺮوﻫﻲ ﻻﻛﺘﺎت ﻫﺮ ﺳﻪ ﮔﺮوه ﻣﻌﻨﻲدار ﻧﻴﺴﺖ ).(P>0/05
35
در زﻧﺎن و ﻫﻢ در ﻣﺮدان ﻛﺎﻫﺶ ﻣﻲﻳﺎﺑﺪ .ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ اﻳﻦ ﻣﺒﺎﺣﺚ ﺷﺎﻳﺪ ﺣﺠﻢ و ﺷﺪت ﺗﻤﺮﻳﻦ در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﺑﻪ اﻧﺪازه ﻛـﺎﻓﻲ ﺑـﺎﻻ ﻧﺒـﻮده ﻳـﺎ
ﺑﺤﺚ
ﺣﺮﻛﺎت اﻧﺠﺎم ﺷﺪه ﺗﻮده ﻋﻀﻼﻧﻲ ﺑـﺰرگ را ﺑـﻪ اﻧـﺪازه ﻛـﺎﻓﻲ ﺑـﻪ ﻛـﺎر ﻧﮕﺮﻓﺘﻨــﺪ ﺗــﺎ ﺳــﺒﺐ ﺗﻐﻴﻴــﺮ ﻣﻌﻨــﻲداري در ﺳــﻄﻮح ﺗــﺴﺘﻮﺳﺘﺮون و
ﻧﺘﺎﻳﺞ ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﻧﺸﺎن داد ﻣﺘﻌﺎﻗﺐ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ
دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت ﺑﻴﻦ ﮔﺮوﻫﻲ ﺷﻮد .اﻓﺰاﻳﺶ ﺗﺴﺘﻮﺳﺘﺮون
و ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ ،ﺳـﻄﻮح آﻧـﺪروژنﻫـﺎ )ﺗـﺴﺘﻮﺳﺘﺮون و
در ﺑﺮﺧﻲ ﺗﺤﻘﻴﻘﺎت ﻣﻤﻜﻦ اﺳﺖ ﺑﻪ دﻟﻴﻞ ﻛﺎﻫﺶ ﺣﺠﻢ ﭘﻼﺳﻤﺎ ،ﺗﺤﺮﻳﻚ 48
49
دﻫﻴﺪرواﭘﻲآﻧﺪرﺳﺘﺮون ﺳﻮﻟﻔﺎت( ﺑﻼﻓﺎﺻﻠﻪ و ﭘﺲ از ﮔﺬﺷﺖ 15دﻗﻴﻘـﻪ
آدرﻧﺎﻟﻴﻨﻲ ،اﺛـﺮ ﺗﺤﺮﻳﻜـﻲ ﻻﻛﺘـﺎت و ﻳـﺎ ﺗﻮاﻧـﺎﻳﻲ ﺳـﺎزﮔﺎري ﺗﺮﺷـﺢ
از ﻣﺪاﺧﻠﻪ ﺗﻤﺮﻳﻨﻲ اﻓﺰاﻳﺶ داﺷﺘﻪ اﺳﺖ وﻟﻲ اﻳﻦ اﻓـﺰاﻳﺶ ﺑـﻪ اﻧـﺪازهاي
ﺗﺴﺘﻮﺳﺘﺮون ﺑﺎﺷﺪ 50.ﭘﮋوﻫﺸﮕﺮان ﻧﺸﺎن دادهاﻧﺪ ﻛـﻪ ﭘﺎﺳـﺦ ﺗـﺴﺘﻮﺳﺘﺮون
ﻧﺒﻮده ﻛﻪ ﺑﺘﻮاﻧﺪ ﺑﺮ ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﺗﺎﺛﻴﺮﮔـﺬار ﺑﺎﺷـﺪ .ﺑـﺎ اﻳـﻦ ﻛـﻪ
29
ﺑﻪ ﺗﻤﺮﻳﻦ در اﻓﺮاد ﺗﻤﺮﻳﻦ ﻛﺮده ﻧﺴﺒﺖ ﺑﻪ ﺗﻤﺮﻳﻦ ﻧﻜﺮده ﺑـﺎﻻﺗﺮ اﺳـﺖ.
ﺗﺤﻘﻴﻘــﺎت در اﻳــﻦ زﻣﻴﻨــﻪ ﻣﺤــﺪود اﺳــﺖ ،ﺑﻌــﻀﻲ از آنﻫــﺎ اﻓــﺰاﻳﺶ
از آنﺟﺎ ﻛﻪ آزﻣﻮدﻧﻲﻫﺎي ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﻏﻴﺮ ورزﺷﻜﺎر ﺑﻮدﻧﺪ ،ﺷﺎﻳﺪ اﻳﻦ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
دﻧﻴﺎ ﺻﻮرﺗﻲ ﺟﺎﺑﻠﻮ و ﻫﻤﻜﺎران
115
ﻋﺎﻣﻞ دﻟﻴﻞ دﻳﮕﺮ ﺑﺮاي ﻣﻌﻨﻲدار ﻧﺒـﻮدن ﺗﻐﻴﻴـﺮات ﺑـﻴﻦ ﮔﺮوﻫـﻲ ﻣﻘـﺎدﻳﺮ
58
ﻃﻮﻻﻧﻲ ﺑﺎﺷﺪ ،اﻳﻦ ﻋﺎﻣﻞ ﺳﺒﺐ اﻓﺰاﻳﺶ ﻣﻌﻨﻲدار ﻛﻮرﺗﻴﺰول ﻣـﻲﺷـﻮد.
آﻧﺪروژنﻫﺎ ﺑﺎﺷﺪ .ﻫﻢﭼﻨﻴﻦ ﭘﺎﺳﺦ ﻫﻮرﻣـﻮﻧﻲ ﭘـﺎﻳﻴﻦ در زﻧـﺎن ﺑـﻪ دﻟﻴـﻞ
ﻋﻮاﻣﻞ زﻳﺎدي ﻣﺎﻧﻨﺪ ﻓﺸﺎرﻫﺎي ﻓﻴﺰﻳﻮﻟﻮژﻳﻜﻲ ،رﻳﺘﻢ ﺷـﺒﺎﻧﻪروزي ،ﻏـﺬاي
ﺣﺠﻢ ﻛﻢ ﺗﻮده ﻋﻀﻼﻧﻲ درﮔﻴـﺮ در ﻓﻌﺎﻟﻴـﺖ ﻣـﻲﺗﻮاﻧـﺪ ﻋﻠـﺖ دﻳﮕـﺮي
ﺧﻮرده ﺷﺪه ﻳـﺎ ﻧﺎﺷـﺘﺎ ﺑـﻮدن و درﺟـﻪ ﺣـﺮارت ﺑـﺪن ﺑـﺮ ﭘﺎﺳـﺦ ﺣـﺎد
ﺑﺎﺷﺪ 51-53.ﺗﺤﻘﻴﻘﺎت ﻧﺸﺎن دادهاﻧﺪ ﻛﻪ آدرﻧﻮﻛﻮرﺗﻴﻜﻮﺗﺮوﭘﻴﻦ در ﭘﺎﺳﺦ ﺑﻪ
ﻛﻮرﺗﻴﺰول ﺑﻪ ﻳﻚ ﺟﻠﺴﻪ ﺗﻤﺮﻳﻦ ﺗـﺄﺛﻴﺮ ﻣـﻲﮔﺬارﻧـﺪ 59.ﻧـﺸﺎن داده ﺷـﺪه
ﺗﻤﺮﻳﻦ ﺷﺪﻳﺪ اﻓﺰاﻳﺶ ﻣﻲﻳﺎﺑﺪ ﻛﻪ ﻣﻲﺗﻮاﻧﺪ ﺑﻪﻧﻮﺑﻪ ﺧـﻮد ﻣﻮﺟـﺐ ﺗﺮﺷـﺢ
اﺳﺖ ﻛﻪ ﻛﻮرﺗﻴﺰول در ﻓﻌﺎﻟﻴﺖﻫﺎﻳﻲ ﻛﻪ ﻣﻮﺟـﺐ ﻫﻴﭙﻮﻛـﺴﻲ ﻣـﻲﺷـﻮﻧﺪ
ﺑﻴﺶﺗﺮ ﺗﺴﺘﻮﺳﺘﺮون ﺗﻮﺳﻂ ﻏـﺪد ﻓـﻮق ﻛﻠﻴـﻪ ﺷـﻮد 54.از ﺳـﻮي دﻳﮕـﺮ
ﻧﺴﺒﺖ ﺑﻪ ﻓﻌﺎﻟﻴـﺖﻫـﺎﻳﻲ ﻛـﻪ ﻣﻮﺟـﺐ ﻫﻴﭙﻮﻛـﺴﻲ ﻧﻤـﻲﺷـﻮﻧﺪ اﻓـﺰاﻳﺶ
ﻣﺸﺨﺺ ﺷﺪه ﻛﻪ ﺗﺎرﻫﺎي ﻋﻀﻠﻪ اﺳﻜﻠﺘﻲ داراي ﮔﻴﺮﻧﺪهﻫﺎي اﺧﺘـﺼﺎﺻﻲ
ﺑﻴﺶﺗﺮي ﻣﻲﻳﺎﺑﺪ 60.ﺑﻨـﺎﺑﺮاﻳﻦ اﺣﺘﻤـﺎل دارد اﻓـﺰاﻳﺶ ﻛـﻮرﺗﻴﺰول در اﺛـﺮ
آﻧﺪروژن ﻫﺴﺘﻨﺪ ﻛﻪ ﻣﻲﺗﻮاﻧﻨﺪ ﺑﺎ ﻣﺘﺎﺑﻮﻟﻴﺰه ﻛﺮدن اﻳﻦ ﻫﻮرﻣﻮنﻫﺎ ﻣﻮﺟـﺐ
ﺗﻤﺮﻳﻦ اﺳﺘﻘﺎﻣﺘﻲ در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﺑﻪ دﻟﻴﻞ ﻣﺪت زﻣﺎن ﻧﺴﺒﺘﺎً ﻃﻮﻻﻧﻲ آن
اﻓﺰاﻳﺶ ﺑﺮداﺷﺖ و ﭘﺎكﻛﻨﻨﺪﮔﻲ آنﻫـﺎ از ﮔـﺮدش ﺧـﻮن ﺷـﻮﻧﺪ 55و از
ﺑﻮده ﻛﻪ ﻣﻮﺟﺐ ﻫﻴﭙﻮﻛﺴﻲ ﺷﺪه اﺳﺖ .اﮔﺮﭼﻪ ﺳـﻄﻮح زﻳـﺎد و ﻃـﻮﻻﻧﻲ
56
ﻣﺪت ﻛﻮرﺗﻴﺰول ﻣﻤﻜﻦ اﺳﺖ اﺛﺮات زﻳﺎنآور داﺷﺘﻪ ﺑﺎﺷﺪ ،اﻣـﺎ اﻓـﺰاﻳﺶ
ﺗﺨﺮﻳﺐ ﭘﺮوﺗﻴﻴﻦ ﻋﻀﻼت اﺳﻜﻠﺘﻲ ﺑﻪ ﻫﻨﮕﺎم ﺗﻤﺮﻳﻦ ﺟﻠـﻮﮔﻴﺮي ﻛﻨﻨـﺪ.
61
ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻧﻜﺎت ذﻛﺮ ﺷﺪه ،در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﺷﺎﻳﺪ اﻓـﺰاﻳﺶ ﺑﺮداﺷـﺖ
ﺣﺎد آن ،ﺑﺨﺸﻲ از روﻧﺪ ﺷﻜﻞﮔﻴﺮي ﭘﺮوﺳﻪ رﺷﺪ ﻋﻀﻠﻪ ﻣﻲﺑﺎﺷـﺪ .در
ﺗﺴﺘﻮﺳﺘﺮون ﺗﻮﺳﻂ ﻋﻀﻼت ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﻧﺎﻣﺤـﺴﻮس ﺗـﺴﺘﻮﺳﺘﺮون
ﺗﺤﻘﻴﻖ Hakkinenدر زﻧﺎن ﻣﺴﻦ ،ﻣﻘـﺎدﻳﺮ ﻛـﻮرﺗﻴﺰول ﻣﺘﻌﺎﻗـﺐ ﺗﻤـﺮﻳﻦ
ﺑﺎﺷﺪ .ﻫﻢﭼﻨـﻴﻦ ﺑـﺎ ﺗﻮﺟـﻪ ﺑـﻪ اﻳـﻦ ﻛـﻪ در ﺗﺤﻘﻴـﻖ Copelandﻣﻘـﺎدﻳﺮ
ﻣﻘﺎوﻣﺘﻲ ﺗﻐﻴﻴﺮي ﻧﻴﺎﻓﺖ ﻛﻪ ﺑﺎ ﻧﺘﺎﻳﺞ ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﻫﻢﺧﻮاﻧﻲ دارد .اﻳﺠﺎد
ﺗﺴﺘﻮﺳﺘﺮون ﺑﻌﺪ از ﻫﺮ دو ﻧﻮع ﺗﻤـﺮﻳﻦ ﻣﻘـﺎوﻣﺘﻲ و اﺳـﺘﻘﺎﻣﺘﻲ اﻓـﺰاﻳﺶ
ﭘﺎﺳﺦ ﻛﻮرﺗﻴﺰول ﺑﻪ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﺑـﻪ ﻋـﻮاﻣﻠﻲ ﻣﺎﻧﻨـﺪ درﮔﻴـﺮي ﺗـﻮده
ﻳﺎﻓﺖ اﻣﺎ ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول ﻛﺎﻫﺶ ﻳﺎﻓﺖ ،ﺑﻨﺎﺑﺮاﻳﻦ ﺷﺎﻳﺪ اﻓـﺰاﻳﺶ
ACTH
44و34
ﻋﻀﻼﻧﻲ ﺑﺰرگ ،ﺷﺪت و ﺣﺠـﻢ ﺑـﺎﻻي ﺗﻤـﺮﻳﻦ ﺑـﺴﺘﮕﻲ دارد.
در
در زﻧﺎن ﻣﺴﻦ ﻣﺤﺮك ﻗﻮي ﺑﺮاي اﻓـﺰاﻳﺶ ﺗﺮﺷـﺢ ﺗـﺴﺘﻮﺳﺘﺮون ﻧﺒﺎﺷـﺪ.
ﺻﻮرﺗﻲ ﻛﻪ ﻣﺪت زﻣﺎن اﺳﺘﺮاﺣﺖ ﺑـﻴﻦ ﺳـﺖﻫـﺎ ﻛـﺎﻫﺶ ﻳﺎﺑـﺪ ،ﭘﺎﺳـﺦ
ﻣﻄﺎﻟﻌﺎت ﻧﺸﺎن دادهاﻧﺪ ﻛﻪ اﻓﺰاﻳﺶ ﻻﻛﺘﺎت ﻣﺘﻌﺎﻗـﺐ ﺗﻤﺮﻳﻨـﺎت ورزﺷـﻲ
ﻛﻮرﺗﻴﺰول ﺑﻪ ﺗﻤﺮﻳﻦ ﻗﺎﺑﻞ ﺗﻮﺟﻪ اﺳﺖ 34زﻳﺮا ﻛـﺎﻫﺶ زﻣـﺎن اﺳـﺘﺮاﺣﺖ 35
ﺷﺪﻳﺪ ﺑﺎ اﺛﺮ ﺗﺤﺮﻳﻜﻲ ﺑﺮ ﺗﺮﺷﺢ ﮔﻨﺎدﻫﺎ و ﺑﻪ دﻧﺒـﺎل آن اﻓـﺰاﻳﺶ رﻫـﺎﻳﺶ
ﺑﻴﻦ ﺳﺖﻫﺎ ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﻓﺸﺎر ﺗﻤﺮﻳﻦ ﻣﻲﺷﻮد .ﺑﺮاي اﻳﺠﺎد اﻓﺰاﻳﺶ
ﻫﻮرﻣﻮن ﻟﻮﺗﻴﻴﻨﻲ از ﻫﻴﭙﻮﻓﻴﺰ ﻗﺪاﻣﻲ ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﺗﺮﺷﺢ ﺗـﺴﺘﻮﺳﺘﺮون
در ﻛــﻮرﺗﻴﺰول ،ﺷــﺪت ﺗﻤــﺮﻳﻦ ﻣﻘــﺎوﻣﺘﻲ ﺑﺎﻳــﺪ ﺑــﻪ اﻧــﺪازه ﻛــﺎﻓﻲ زﻳــﺎد 42و39و32
ﻣﻲﺷﻮد 56.ﺑﻨﺎﺑﺮاﻳﻦ ﺷﺎﻳﺪ ﻣﻌﻨﻲدار ﻧﺒﻮدن ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫـﻲ ﻣﻘـﺎدﻳﺮ
ﺑﺎﺷﺪ.
آﻧﺪروژنﻫﺎ در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ﺑﻪ دﻟﻴﻞ اﻓﺰاﻳﺶ ﻛﻢ ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت ﺧـﻮن
ﻣﻘﺎوﻣﺘﻲ ﺑﻪ اﻧﺪازه ﻛﺎﻓﻲ زﻳﺎد ﻧﺒﻮده ﺗﺎ ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﺑﻴﺶﺗﺮ ﻛﻮرﺗﻴﺰول
در ﭘﻲ ﺗﻤﺮﻳﻨﺎت آﺳﺘﺎﻧﻪ و زﻳﺮ آﺳﺘﺎﻧﻪ ﺑﺎﺷﺪ.
ﺷﻮد .ﻫﻢﭼﻨﻴﻦ ﻣﻤﻜﻦ اﺳﺖ ﺗﻤﺮﻳﻦ ﻣﻘﺎوﻣﺘﻲ ﻣﻮﺟﺐ ﻫﻴﭙﻮﻛﺴﻲ ﻧﺸﺪه ﺗـﺎ
ﺑﻨﺎﺑﺮاﻳﻦ ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ،ﺷﺪت ﺗﻤـﺮﻳﻦ
ﻧﺘﺎﻳﺞ اﻳﻦ ﺗﺤﻘﻴﻖ ﻧﺸﺎن داد ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﻛـﻮرﺗﻴﺰول
ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﺑـﻴﺶﺗـﺮ ﻛـﻮرﺗﻴﺰول ﻣﻬﻴـﺎ ﺷـﻮد .در ﭘـﮋوﻫﺶ ﺣﺎﺿـﺮ
ﻣﻌﻨﻲدار اﺳﺖ .ﺑﻪ ﻋﺒﺎرت دﻳﮕﺮ ﺗﻨﻬﺎ در ﻧﺘﻴﺠﻪ ﻣﺪاﺧﻠﻪ ﺗﻤﺮﻳﻦ اﺳـﺘﻘﺎﻣﺘﻲ
ﺗﻐﻴﻴــﺮات درون ﮔﺮوﻫــﻲ ﻻﻛﺘــﺎت ﺧــﻮن ﻣﺘﻌﺎﻗــﺐ ﺗﻤــﺮﻳﻦ ﻣﻘــﺎوﻣﺘﻲ و
ﻣﻘﺎدﻳﺮ ﻛﻮرﺗﻴﺰول اﻓﺰاﻳﺶ ﻳﺎﻓـﺖ .ﺗﻐﻴﻴـﺮات ﻛـﻮرﺗﻴﺰول ﺳـﺮم ﺑـﻪ ﻧـﻮع،
اﺳﺘﻘﺎﻣﺘﻲ ﻣﻌﻨﻲدار اﺳﺖ در ﺻﻮرﺗﻲ ﻛﻪ اﻓﺰاﻳﺶ آﻧـﻲ و ﻛـﺎﻫﺶ ﺳـﺮﻳﻊ
ﺷﺪت و ﻣﺪت ﻓﻌﺎﻟﻴﺖ ﺑﺴﺘﮕﻲ دارد ،ﺑﻪ ﻃﻮري ﻛﻪ ﻓﻌﺎﻟﻴﺖ ﺑﺪﻧﻲ ﺑﻴﺶ از
ﻻﻛﺘﺎت ﺑﻼﻓﺎﺻﻠﻪ و ﭘﺲ از ﮔﺬﺷﺖ 15دﻗﻴﻘـﻪ از ﺗﻤـﺮﻳﻦ ﺑـﻪ اﻧـﺪازهاي
%60ﺣﺪاﻛﺜﺮ اﻛﺴﻴﮋن ﻣﺼﺮﻓﻲ از ﻣﻬـﻢﺗـﺮﻳﻦ ﻣﺤـﺮكﻫـﺎي ﺗﺮﺷـﺢ اﻳـﻦ
ﻧﻴﺴﺖ ﻛﻪ ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻻﻛﺘﺎت ﻫﺮ ﺳﻪ ﮔـﺮوه ﻣﻌﻨـﻲدار ﺷـﻮد،
ﻫﻮرﻣﻮن اﺳﺖ .ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ ﻓﻌﺎﻟﻴﺖ ﺟﺴﻤﺎﻧﻲ ﺷﺪﻳﺪ ﻣﻮﺟﺐ اﻓﺰاﻳﺶ
اﻳﻦ ﻳﺎﻓﺘﻪ ﺑﺎ ﻧﺘﺎﻳﺞ ﺗﺤﻘﻴﻘـﺎت Copelandو Hakkinenﻫـﻢﺧـﻮاﻧﻲ دارد.
ﺗﺮﺷﺢ ACTHو در ﻧﺘﻴﺠـﻪ اﻓـﺰاﻳﺶ ﺗﺮﺷـﺢ ﻛـﻮرﺗﻴﺰول ﺷـﻮد .اﻓـﺰاﻳﺶ
ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت ﺧﻮن ﺑﻪ ﻃﻮر ﻣﻌﻨﻲداري ﺗﺤﺖ ﺗﺄﺛﻴﺮ ﺷﺪت ﺗﻤﺮﻳﻦ ﻗـﺮار
ﻛﻮرﺗﻴﺰول ﺗﻨﻬﺎ ﺑﻪ ﺷﺪت ﻓﻌﺎﻟﻴﺖ ﺟﺴﻤﺎﻧﻲ ﺑـﺴﺘﮕﻲ ﻧـﺪارد ﺑﻠﻜـﻪ ﻣـﺪت
51
ﻣﻲﮔﻴﺮد .ﻋﻼوه ﺑﺮ اﻳﻦ ﻧﺸﺎن دادهاﻧﺪ ﻛﻪ ﭘﺎﺳﺦ ﻻﻛﺘـﺎت ﺑـﻪ ﺗﻤـﺮﻳﻦ در 18
ﻓﻌﺎﻟﻴﺖ ﺟﺴﻤﺎﻧﻲ ﻳﺎ ﺗﻌﺎﻣﻞ ﻫﺮ دو ﺑﺎ ﻫﻢ ﻧﻴـﺰ ﻣـﺆﺛﺮ ﻣـﻲﺑﺎﺷـﻨﺪ .درﺳـﺖ
اﻓﺮاد ﻣﺴﻦ ،ﻧﺴﺒﺖ ﺑﻪ ﺟﻮاﻧﺎن ﻛﻢﺗﺮ اﺳﺖ .دﻟﻴـﻞ اﻳـﻦ اﻣـﺮ را ﻇﺮﻓﻴـﺖ
اﺳﺖ ﻛﻪ ﻣﻴﺰان ﻛﻮرﺗﻴﺰول ﻣﺘﻨﺎﺳﺐ ﺑﺎ ﺷﺪت ﻓﻌﺎﻟﻴﺖ ﺟـﺴﻤﺎﻧﻲ اﻓـﺰاﻳﺶ
ﻛﻢﺗﺮ اﻓﺮاد ﻣﺴﻦ در ﺗﻮاﻧﺎﻳﻲ ﺗﺤﻤﻞ ﻓﺸﺎر ﺗﻤﺮﻳﻦ داﻧﺴﺘﻪاﻧﺪ ،اﻓـﺮاد ﻣـﺴﻦ
ﻣﻲﻳﺎﺑﺪ اﻣﺎ ﺣﺪاﻛﺜﺮ اﻓﺰاﻳﺶ ﻛﻮرﺗﻴﺰول ﺑﻪ ﻣﺪت زﻣـﺎن ﻓﻌﺎﻟﻴـﺖ ﺑـﺴﺘﮕﻲ
ﻗﺎدر ﺑﻪ اﻧﺠﺎم ﺗﻤﺮﻳﻦ ﺑﺎ ﺷﺪت ﭘﺎﻳﻴﻦﺗﺮ ﻣﻲﺑﺎﺷﻨﺪ ،ﻫﻢﭼﻨـﻴﻦ ﻛﺎﻫـﺸﻲ در
دارد 57،ﺣﺘﻲ اﮔﺮ ﺷﺪت ﻓﻌﺎﻟﻴﺖ زﻳﺎد ﻧﺒﺎﺷﺪ وﻟﻲ ﻓﻌﺎﻟﻴﺖ ﺑﻪ اﻧﺪازه ﻛـﺎﻓﻲ
اوج ﻻﻛﺘﺎت ﺧﻮن ﻃﻲ ﺗﻤﺮﻳﻦ ،ﻫﻤﺮاه ﺑﺎ اﻓﺰاﻳﺶ ﺳﻦ اﻳﺠﺎد ﻣﻲﺷﻮد ﻛـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
Sourati D. et وal.ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻨﺎت ﻣﻘﺎوﻣﺘﻲ ﻛﻮرﺗﻴﺰول و ﻻﻛﺘﺎت زﻧﺎن،ﻫﺎ آﻧﺪروژنJabloo اﺳﺘﻘﺎﻣﺘﻲ ﺑﺮ
116
ﺗﺎﺛﻴﺮي ﻣﻄﻠﻮب ﺑﺮ ﺳﻼﻣﺖ ﺑﺎﻓﺖ،در ﺳﻄﻮح ﭘﺎﻳﻪ ﻫﻮرﻣﻮنﻫﺎي آﻧﺎﺑﻮﻟﻴﻚ
اﻳﻦ اﻣﺮ ﻧﺎﺷﻲ.ﺑﺎ ﻛﻢ ﺷﺪن ﻇﺮﻓﻴﺖ ﮔﻠﻴﻜﻮﻟﻴﺘﻴﻜﻲ ﻋﻀﻠﻪ در ارﺗﺒﺎط اﺳﺖ
ﺑﺎ اﻳﻦ ﻛﻪ اﻧﺠﺎم ﺗﻤﺮﻳﻨﺎت ﻣﻘﺎوﻣﺘﻲ ﺑﻪ ﻋﻨﻮان روش ﻏﻴﺮ داروﻳﻲ.ﺑﮕﺬارﻧﺪ
ﮔﻠﻴﻜـﻮﻟﻴﺘﻴﻜﻲ و ﻛﺎﻫــﺶIIB از آﺗﺮوﻓﻲ ﻋﻀﻼﻧﻲ اﻧﺘﺨﺎﺑﻲ ﺗﺎرﻫﺎي ﻧﻮع
،ﺑﺮاي ﺣﻔﻆ ﺳﻄﻮح ﺑﻬﻴﻨﻪ آﻧﺪروژنﻫـﺎ و ﻛـﻮرﺗﻴﺰول ﭘﻴـﺸﻨﻬﺎد ﻣـﻲﺷـﻮد
ﻓﻌﺎﻟﻴﺖ ﻻﻛﺘﺎت دﻫﻴـﺪروژﻧﺎز ﻋـﻀـﻼﻧﻲ و ﻛﺎﻫــﺶ در ﺣـﺴﺎﺳﻴﺖ ﺑـﻪ
ﺗﺤﻘﻴﻘﺎت ﺑﻴﺶﺗﺮي ﻻزم اﺳﺖ ﺗﺎ ﺗﺄﺛﻴﺮ ﺗﻤﺮﻳﻦ ﺑﺮ ﺳﻄﻮح ﻫﻮرﻣـﻮنﻫـﺎي
ﺑﻨـﺎﺑﺮاﻳﻦ62.آدرﻧﺎﻟﻴـﻦ ﻣﻲﺑﺎﺷﺪ ﻛـﻪ ﻫﻤـﺮاه ﺑﺎ اﻓﺰاﻳـﺶ ﺳـﻦ رخ ﻣﻲدﻫﺪ
آﻧﺎﺑﻮﻟﻴﻚ دﻳﮕـﺮ ﻧﻈﻴـﺮ ﻫﻮرﻣـﻮن رﺷـﺪ و ﻓـﺎﻛﺘﻮر رﺷـﺪ ﺷـﺒﻪ اﻧـﺴﻮﻟﻴﻦ
ﻣﻌﻨﻲدار ﻧﺒﻮدن ﺗﻐﻴﻴﺮات ﺑﻴﻦ ﮔﺮوﻫﻲ ﻣﻘﺎدﻳﺮ ﻻﻛﺘﺎت در ﺗﺤﻘﻴـﻖ ﺣﺎﺿـﺮ
.ﺑﺮرﺳﻲ ﮔﺮدد
ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺿﺮورت ﺣﻔﻆ ﺑﻬﻴﻨﻪ ﺳﻄﻮح.ﺷﺎﻳﺪ ﺑﻪ دﻻﻳﻞ ذﻛﺮ ﺷﺪه ﺑﺎﺷﺪ
اﻧﺠـﺎم اﻳـﻦ، ﺑﺎ ﺗﻘﺪﻳﺮ از ﻣﺎدراﻧﻲ ﻛﻪ ﻣﺎ را ﻳﺎري دادﻧﺪ:ﺳﭙﺎﺳﮕﺰاري
آﻧﺪروژنﻫﺎ و ﻛﻮرﺗﻴﺰول در زﻧﺎن ﻣﺴﻦ و اﻫﻤﻴﺖ ﺣﻔﻆ ذﺧﺎﻳﺮ ﭘﺮوﺗﻴﻴﻨﻲ
ﺗﺤﻘﻴﻖ ﺑﺎ ﺣﻤﺎﻳﺖ ﻣﻌﺎوﻧـﺖ ﭘﮋوﻫـﺸﻲ داﻧـﺸﮕﺎه ﻓﺮدوﺳـﻲ و ﻫﻤﻜـﺎري
ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ ﺗﻤﺮﻳﻨـﺎت ﻣﻘـﺎوﻣﺘﻲ ﻳـﻚ،ﻋﻀﻼت ﻃﻲ ﻓﺮاﻳﻨﺪ ﭘﻴﺮﺷﺪن
ﻣﻌﺎوﻧﺖ ﭘﮋوﻫﺸﻲ واﺣﺪ ﺟﻬﺎد داﻧﺸﮕﺎﻫﻲ ﻣﺸﻬﺪ ﻣﻴﺴﺮ ﮔﺮدﻳﺪ ﻛﻪ ﺑـﺪﻳﻦ
روش ﻣﻔﻴﺪ ﺑﺮاي ﺣﻔﻆ و ﺣﺘﻲ اﻓﺰاﻳﺶ ﺗﻮده ﻋـﻀﻼﻧﻲ در زﻧـﺎن ﻣـﺴﻦ
.وﺳﻴﻠﻪ از آنﻫﺎ ﻗﺪرداﻧﻲ ﻣﻲﮔﺮدد
ﺷﻮاﻫﺪ ﻧﺸﺎن ﻣﻲدﻫﻨﺪ ﺗﻤﺮﻳﻨﺎت ورزﺷﻲ ﻣﻲﺗﻮاﻧﻨﺪ ﺑﺪون اﻓـﺰاﻳﺶ.ﺑﺎﺷﺪ
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Tehran University Medical Journal; Vol. 70, No. 2, May 2012: 110-118
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Effects of resistance and endurance exercises on androgens, cortisol and lactate in elderly women
Abstract Donya Sourati Jabloo M.Sc.1 Seyyed Reza Attarzadeh Hosseini Ph.D.1* Delaram Sayadpour Zanjani Ph.D.2 Amin Ahmadi M.Sc.1 1- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. 2- Department of Pathology, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad, Iran.
Received: September 17, 2011 Accepted: January 29, 2012
Background: The basal levels of androgens in women decline gradually with age. These changes may reduce muscle strength and bone density leading to fatigue and psychological problems. Thus, the aim of this study was to compare the effects of resistance and endurance exercises on androgens, cortisol and lactate concentrations in elderly women. Methods: In this study, 10 elderly women with a mean age of 54.3±3.74 years and a BMI of 24.88±2.07 kg/m2 completed an endurance exercise session (ES), a resistance exercise session (RS), and a control session (CS) in a randomized, cross-balanced design. The RS consisted of three sets of 10 repetitions of eight exercises with 80% 1RM (one repetition maximum) over of 45 minutes and the ES consisted of cycling at 60%-70% of maximum oxygen consumption for 45 minutes. During the CS, subjects performed no exercise. Before and immediately after exercises, and after 15 minutes of recovery, and also during CS blood samples were obtained an analyzed for serum testosterone, dehydroepiandrosterone sulfate, cortisol and lactate. Results: There was a significant increase in testosterone levels following resistance and endurance exercise sessions (P<0.05). Dehydroepiandrosterone sulfate demonstrated a significant increase after resistance exercise (P<0.05). While differences in cortisol levels were not significant within groups, but they were significant (P<0.05) between groups. Conclusion: A session of resistance exercise in elderly women can increase concentrations of androgens that are essential for their health and well-being. Keywords: Androgen, elderly women, health benefits, resistance exercise.
*
Corresponding author: Faculty of Physical Education and Sport Sciences, Ferdowsi University of Mashhad, Paradise Daneshgah, Azadi Sq., Mashhad, Iran. Tel: +98- 511- 8833910 E-mail: attarzadeh@um.ac.ir
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-125 ،1391 ﻣﻔﺼﻠ 2 داﺧﻞﺷﻤﺎره دورهﻲ ، ،70 دﻛﺴﺘﺮوزﺗﻬﺮان، ﻋﻠﻮم ﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﭘﺰﺷﻜﻲ، داﻧﺸﻜﺪه 119زاﻧﻮ اﺳﺘﺌﻮآرﺗﺮﻳﺖ اردﻳﺒﻬﺸﺖدرد ﻲ ،در درﻣﺎن ﭘﺮوﻟﻮﺗﺮاﭘ اﺳﻴﺪ و ﺎﻟﻮروﻧﻴﻚ ﺗﺎﺛﻴﺮ ﻫﻴ ﻣﺠﻠﻪﻣﻘﺎﻳﺴﻪ
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ﻣﻘﺎﻳﺴﻪ ﺗﺎﺛﻴﺮ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧﻞ ﻣﻔﺼﻠﻲ در درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/08/14 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/10/21 :
ﺳﻴﺪ ﻣﺴﻌﻮد ﻫﺎﺷﻤﻲ
ﭼﻜﻴﺪه
*1 1
ﻓﻴﺮوز ﻣﺪدي 2،ﺳﻌﻴﺪ رﺿﻮي
زﻣﻴﻨﻪ و ﻫﺪف :در درﻣﺎن اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ﻗﺒﻞ از ﺟﺮاﺣﻲ از درﻣﺎنﻫﺎي ﻧﮕﻪدارﻧﺪه اﺳﺘﻔﺎده ﻣـﻲﺷـﻮد .در اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ
3
ﻣﻬﺸﻴﺪ ﻧﻴﻜﻮﺳﺮﺷﺖ
اﺛﺮات ﻛﻮﺗﺎهﻣﺪت ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧـﻞ ﻣﻔـﺼﻠﻲ در ﺑﻬﺒـﻮد درد و ﻋﻤﻠﻜـﺮد زاﻧـﻮ و ﻛﻴﻔﻴـﺖ
1
ﻓﺮﺷﺎد ﺣﺴﻦ زاده ﻛﻴﺎﺑﻲ
زﻧﺪﮔﻲ در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ارزﻳﺎﺑﻲ و ﻣﻘﺎﻳﺴﻪ ﺷﺪ .روش ﺑﺮرﺳﻲ :اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑـﻪﺻـﻮرت ﻛﺎرآزﻣـﺎﻳﻲ
4
ﺳﻤﻴﻪ ﻧﺼﻴﺮي ﭘﻮر
ﺑﺎﻟﻴﻨﻲ دوﺳﻮﻛﻮر اﻧﺠﺎم ﺷﺪ .از 100ﺑﻴﻤﺎر ﺑﺎ ﺳﻦ 40-70ﺳﺎل ،ﻛـﻪ ﺑـﺮ اﺳـﺎس ﻛﺮاﻳﺘﺮﻳـﺎي ACRﺑـﺮاي آنﻫـﺎ ﺗـﺸﺨﻴﺺ -1ﮔﺮوه ﺑﻴﻬﻮﺷﻲ و درد ،ﺑﻴﻤﺎرﺳﺘﺎن اﺧﺘﺮ ،داﻧﺸﮕﺎه
اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ داده ﺷﺪه ﺑﻮد و ﺑﻴﺶ از ﺳﻪ ﻣﺎه درد داﺷﺘﻨﺪ 50 ،ﺑﻴﻤﺎر در ﮔﺮوه ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ 2ml ،ﺗﺰرﻳﻖ داﺧـﻞ
ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺷﻬﻴﺪﺑﻬﺸﺘﻲ ،ﺗﻬﺮان ،اﻳﺮان.
ﻣﻔﺼﻠﻲ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ )ﺳﻴﻨﻮﻛﺮوم ﻓﻮرت (%1ﭘﻨﺞ ﺟﻠﺴﻪ ﻫﻔﺘﻪاي ﻳﻚﺑﺎر و 50ﺑﻴﻤﺎر در ﮔﺮوه دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ،
-2ﮔﺮوه ارﺗﻮﭘﺪي ،ﺑﻴﻤﺎرﺳﺘﺎن اﺧﺘﺮ ،داﻧﺸﮕﺎه ﻋﻠﻮم
در ﺳﻪ ﺟﻠﺴﻪ ﻣﺎﻫﻴﺎﻧﻪ 2mlﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﺎ دﻛﺴﺘﺮوز %25درﻳﺎﻓﺖ ﻛﺮدﻧﺪ .ﺑﻴﻤـﺎران ﻗﺒـﻞ و ﭘـﺲ از درﻣـﺎن از ﻧﻈـﺮ درد و
ﭘﺰﺷﻜﻲ ﺷﻬﻴﺪﺑﻬﺸﺘﻲ ،ﺗﻬﺮان ،اﻳﺮان.
ﻋﻤﻠﻜﺮد زاﻧﻮ ﺑﺎ اﺳﺘﻔﺎده از ﭘﺮﺳﺶﻧﺎﻣﻪ KOOSﺑﺮرﺳﻲ ﺷﺪﻧﺪ .ﺑﻴﻤﺎران ﺗﻮﺳﻂ ﻓﺮد ﻏﻴﺮ ﻣﻄﻠﻊ از ﻧﻮع درﻣﺎن 12ﻫﻔﺘﻪ ﭘﺲ از
-3ﮔﺮوه ﺑﻴﻬﻮﺷﻲ و درد ،ﺑﻴﻤﺎرﺳﺘﺎن ﺑﻌﺜﺖ، داﻧﺸﮕﺎه ﻋﻠﻮمﭘﺰﺷﻜﻲ ﻫﻤﺪان ،ﻫﻤﺪان ،اﻳﺮان.
ﺗﺰرﻳﻖ ارزﻳﺎﺑﻲ ﺷﺪﻧﺪ .ﺳﭙﺲ اﻃﻼﻋﺎت ﺣﺎﺻﻠﻪ از ﺑﻴﻤﺎران ﺛﺒـﺖ ﺷـﺪﻧﺪ .ﻳﺎﻓﺘـﻪﻫـﺎ :ﻣﻴـﺎﻧﮕﻴﻦ ﺳـﻦ اﻓـﺮاد ﻣـﻮرد ﺑﺮرﺳـﻲ
-4ﮔﺮوه داروﺳﺎزي ﺑﺎﻟﻴﻨﻲ ،داﻧﺸﻜﺪه داروﺳﺎزي،
60/6±8/2ﺳﺎل ﺑﻮد .ﺗﻔﺎوت ﻣﻌﻨﻲداري ﺑﻴﻦ دو ﮔﺮوه در اﺳـﻜﻮرﻫﺎي درد زاﻧـﻮ و ﻋﻤﻠﻜـﺮد آن دﻳـﺪه ﻧـﺸﺪ ).(P<0/05
داﻧﺸﮕﺎه ﻋﻠﻮمﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان.
اﺳﻜﻮرﻫﺎي ﺗﻤﺎم ﻣﻮارد ﭘﺮﺳﺶﻧﺎﻣﻪ KOOSﭘﺲ از درﻣﺎن ﺑﻬﺒﻮد ﻣﻌﻨﻲداري را ﻧﺸﺎن داد ) .(P<0/001ﺗﻐﻴﻴـﺮات اﺳـﻜﻮرﻫﺎ ﻧﺴﺒﺖ ﺑﻪ ﻣﻴﺰان ﭘﺎﻳﻪ ﭘﺲ از درﻣﺎن ﺑﻴﻦ دو ﮔﺮوه ﺗﻔﺎوت ﻣﻌﻨﻲداري را ﻧﺸﺎن ﻧﺪاد ) .(P<0/05ﻧﺘﻴﺠﻪﮔﻴﺮي :ﺑﻪﻧﻈﺮ ﻣﻲرﺳﺪ، ﺗﺰرﻳﻖ داﺧﻞ ﻣﻔﺼﻠﻲ دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ %25ﺑﻪ اﻧﺪازه ﻫﻴﺎﻟﻮروﻧﻴـﻚ اﺳـﻴﺪ )ﺳـﻴﻨﻮﻛﺮوم ﻓـﻮرت (%1در درﻣـﺎن درد
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ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،اﻟﻬﻴﻪ ،ﺑﻴﻤﺎرﺳﺘﺎن اﺧﺘﺮ ،ﺑﺨﺶ
درد
اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ،ﻣﻮﺛﺮ و اﻳﻤﻦ اﺳﺖ.
ﺗﻠﻔﻦ021-22612252 : E-mail: dr.hashemi@sbmu.ac.ir
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ،ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ،دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ.
ﺑﺎﻻﻳﻲ ﺑﺮﺧﻮردار اﺳـﺖ 3.ﺑـﺎ اﻧﺠـﺎم روزاﻓـﺰون ﺟﺮاﺣـﻲ ﺑـﺮاي درﻣـﺎن
ﻣﻘﺪﻣﻪ
اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ،ﻫﻨﻮز ﺟﻬﺖ اﺟﺘﻨﺎب از اﺛﺮات ﺳﻴﺴﺘﻤﻴﻚ ﻧﺎﺧﻮاﺳـﺘﻪ )Degenerative Joint Disease (DJD
ﻧﻴﺎز ﺑﻪ اﻧﺠﺎم ﻣﺪاﺧﻼت درﻣـﺎﻧﻲ ﻧﮕـﻪدارﻧـﺪه ﺷـﺎﻣﻞ آﻣـﻮزش ﺑﻴﻤـﺎران،
از ﺷﺎﻳﻊﺗﺮﻳﻦ ﺑﻴﻤﺎريﻫﺎي روﻣﺎﺗﻴﺴﻤﻲ در ﺳﺮاﺳﺮ ﺟﻬﺎن ﻣـﻲﺑﺎﺷـﻨﺪ ﻛـﻪ
ﺗﻌﺪﻳﻞ ﻓﻌﺎﻟﻴﺖ ،اﺳﺘﻔﺎده از ﺑﺮﻳﺲ ،داروﻫـﺎي ﺿـﺪ اﻟﺘﻬـﺎﺑﻲ و ﺿـﺪ درد،
ﺷﺎﻳﻊﺗﺮﻳﻦ آنﻫﺎ اﺳﺘﺌﻮآرﺗﺮﻳﺖ ﻣـﻲﺑﺎﺷـﺪ .اﻳـﻦ ﺑﻴﻤـﺎري ﺑـﻪﻃـﻮر ﺷـﺎﻳﻊ
درﻣـﺎنﻫــﺎي ﻓﻴﺰﻳـﻮﺗﺮاﭘﻲ ،ﺗﺰرﻳــﻖ داﺧـﻞ ﻣﻔــﺼﻠﻲ اﺳــﻴﺪﻫﻴﺎﻟﻮروﻧﻴﻚ و
ﺑﻴﻤﺎريﻫﺎي دژﻧﺮاﺗﻴﻮ ﻣﻔﺼﻠﻲ
5و4
ﻣﻔﺎﺻــﻞ ران ،زاﻧــﻮ ،ﺳــﺘﻮن ﻓﻘــﺮات و اﻧﮕــﺸﺘﺎن را درﮔﻴــﺮ ﻣــﻲﻛﻨــﺪ.
ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﺎ دﻛﺴﺘﺮوز ﻣﻲﺑﺎﺷﺪ.
اﺳﺘﺌﻮآرﺗﺮﻳﺖ ﭼﻬـﺎرﻣﻴﻦ ﻋﻠـﺖ ﻧـﺎﺗﻮانﻛﻨﻨـﺪه زﻧـﺪﮔﻲ و %3ﻛـﻞ ﻋﻠـﻞ
اﺳــﻴﺪ و ﻛﻮرﺗﻴﻜﻮاﺳــﺘﺮوﻳﻴﺪﻫﺎ از راﻳــﺞﺗــﺮﻳﻦ روشﻫــﺎي درﻣــﺎﻧﻲ
ﻧﺎﺗﻮانﻛﻨﻨﺪه زﻧﺪﮔﻲ را ﺷﺎﻣﻞ ﻣﻲﺷـﻮد 1.ﺷـﻴﻮع اﺳـﺘﺌﻮآرﺗﺮﻳﺖ زاﻧـﻮ در
اﺳﺘﺌﻮآرﺗﺮﻳﺖ ﺑﻪﺧﺼﻮص در ﺑﻴﻤﺎراﻧﻲ اﺳﺖ ﻛﻪ ﺳﺎﻳﺮ روشﻫﺎي درﻣﺎﻧﻲ
ﺳﻨﻴﻦ ﺑﻴﺶ از 15ﺳﺎل %7/9ﻣﻲﺑﺎﺷﺪ 2.در اﻳـﺮان ﺷـﻴﻮع اﺳـﺘﺌﻮآرﺗﺮﻳﺖ
ﺑﻪدﻟﻴﻞ ﺳﻤﻴﺖ ﻳﺎ ﻋﺪم ﺗﺎﺛﻴﺮ ﺑﺎ ﺷﻜﺴﺖ ﻣﻮاﺟﻪ ﺷـﺪهاﻧـﺪ .در ﺑـﺴﻴﺎري از
زاﻧﻮ در ﺳﻨﻴﻦ ﺑﻴﺶ از 15ﺳﺎل ﺣﺪود %15/34ﻣﻲﺑﺎﺷـﺪ ﻛـﻪ از ﺷﻴـﻮع
ﻣﻄﺎﻟﻌﺎت اﺛﺮات ﻣﻔﻴﺪ ﺗﺰرﻳﻖ داﺧﻞ ﻣﻔﺼﻠﻲ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ در ﻛﻨﺘﺮل
ﺗﺰرﻳﻖ داﺧﻞ ﻣﻔﺼﻠﻲ ﻫﻴﺎﻟﻮروﻧﻴـﻚ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
120
ﺳﻴﺪ ﻣﺴﻌﻮد ﻫﺎﺷﻤﻲ و ﻫﻤﻜﺎران
درد و ﻓﻌﺎﻟﻴﺖ ﺑﻴﻤﺎران ﻧﺸﺎن داده ﺷﺪه اﺳﺖ 6-10.ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﻳﻜﻲ دﻳﮕﺮ
ﻣﺮاﺟﻌﻪ ﻛﻨﻨﺪه ﺑﻪ ﻛﻠﻴﻨﻴﻚ درد ﺑﻴﻤﺎرﺳﺘﺎن اﺧﺘﺮ ﻃﻲ ﺳﺎلﻫﺎي ،1389-90
از روشﻫﺎي درﻣﺎﻧﻲ اﺳﺖ ﻛﻪ ﻣﻨﺠﺮ ﺑﻪ اﻓﺰاﻳﺶ ﻣﻴـﺰان ﻓـﺎﻛﺘﻮر رﺷـﺪ و
100ﻧﻔﺮ ﺑﻪ روش ﻏﻴﺮﺗﺼﺎدﻓﻲ ﺳﺎده اﻧﺘﺨﺎب ﺷﺪﻧﺪ .ﻣﻌﻴﺎر ورود ﺷـﺎﻣﻞ
ﺗــﺎﺛﻴﺮ آن در ﺗــﺮﻣﻴﻢ ﺑﺎﻓــﺖ ﻳــﺎ رﺷــﺪ آن ﻣــﻲﺷــﻮد .ﭘﺮوﻟــﻮﺗﺮاﭘﻲ
ﺳﻦ ﺑﻴﻦ 40ﺗـﺎ 70ﺳـﺎل ،درد اﺳـﺘﺌﻮآرﺗﺮﻳﺖ زاﻧـﻮ ﺑـﻴﺶ از ﺳـﻪ ﻣـﺎه،
) (Prolotherapyاوﻟﻴﻦ ﺑﺎر ﺗﻮﺳﻂ Hackettدر ﺳﺎل 1950ﺗﻮﺻﻴﻒ ﺷﺪ
ﻳﺎﻓﺘــﻪﻫــﺎي رادﻳﻮﻟﻮژﻳــﻚ ﺗﺄﻳﻴــﺪ ﻛﻨﻨــﺪه اﺳــﺘﺌﻮآرﺗﺮﻳﺖ زاﻧــﻮ ﺑﺮاﺳــﺎس 25
)American College of Rheumatology (ACR
و داﺷـﺘﻦ
و ﺑﻪ دﻧﺒﺎل آن ﻣﻄﺎﻟﻌﺎت ﻣﺨﺘﻠﻒ ﺑﺎﻟﻴﻨﻲ ﺑﺮ روي اﻧـﺴﺎن و ﺣﻴـﻮان اﻧﺠـﺎم
ﻛﺮاﻳﺘﺮﻳﺎي
ﺷﺪ 11-16.در دﻛـﺴﺘﺮوز ﭘﺮوﻟـﻮﺗﺮاﭘﻲ ،اﻓـﺰاﻳﺶ ﮔﻠـﻮﻛﺰ ﺧـﺎرج ﺳـﻠﻮﻟﻲ
رﺿﺎﻳﺖ ﻣﺒﻨﻲ ﺑﺮ ﺷﺮﻛﺖ در ﻃﺮح ﺑﻮد .ﺑﻴﻤﺎراﻧﻲ ﻛﻪ رﺿﺎﻳﺖ ﺑﻪ ﺷـﺮﻛﺖ
ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﻓﺎﻛﺘﻮرﻫﺎي رﺷـﺪ ﭼﻨﺪﮔﺎﻧـﻪ ﭘﻠـﻲﭘﭙﺘﻴـﺪ در ﺳـﻠﻮلﻫـﺎي
در ﻃﺮح ﻧﺪاﺷﺘﻨﺪ ،ﺑﻴﻤﺎران ﺑﺎ ﺳﺎﺑﻘﻪ ﺟﺮاﺣﻲ زاﻧﻮ ،دﻓﻮرﻣﻴﺘﻲ و ﻛﻨﺘﺮاﻛﭽﺮ
ﻣﺨﺘﻠﻒ اﻧﺴﺎﻧﻲ ﻣﻲﺷـﻮد 17-21.ﺗﻤـﺎس ﺳـﻠﻮلﻫـﺎي اﻧـﺴﺎﻧﻲ ﺑـﺎ ﻣﺤـﻴﻂ
اﻧﺪام ﺗﺤﺘﺎﻧﻲ ،ﺑﻴﻤﺎري ﻧﻮروﻣﺎﺳﻜﻮﻻر اﻧﺪام ﺗﺤﺘـﺎﻧﻲ ،ﭘـﺎﺗﻮﻟﻮژي ﻛﻤـﺮي
DNA
ﺣﺎد ،ﺗﺰرﻳﻖ داروﻫﺎي اﺳﺘﺮوﻳﻴﺪي ﻃـﻲ دو ﻣـﺎه اﺧﻴـﺮ ،ﺳـﺎﺑﻘﻪ آرﺗﺮﻳـﺖ
ﻓﺎﻛﺘﻮرﻫﺎي رﺷﺪ ﻣﻲﺷـﻮد23.و 22ﻣﺤﻠـﻮل دﻛـﺴﺘﺮوز ﻫﻴﭙﺮﺗﻮﻧﻴـﻚ ﺑـﺎ دو
روﻣﺎﺗﻮﻳﻴﺪ اﻟﺘﻬﺎﺑﻲ ،دﻳﺎﺑﺖ ،ﺣﺎﻣﻠﮕﻲ ،BMI>35 ،ﺑﻴﻤﺎران ﻛﺎﻧﺪﻳﺪ ﺟﺮاﺣـﻲ
ﻣﻜﺎﻧﻴﺴﻢ ﻓﻮق ﻣﻨﺠﺮ ﺑﻪ اﻓﺰاﻳﺶ ﻣﻴﺰان ﻓﺎﻛﺘﻮرﻫﺎي رﺷﺪ ﻣﻲﺷﻮد و داراي
زاﻧﻮ ،وﺟﻮد اﻧﺤﺮاف زاﻧﻮ )واروس ﻳﺎ واﻟﮕﻮس ﺑﻴﺶﺗﺮ از ﭘـﻨﺞ درﺟـﻪ(
ﻗﺎﺑﻠﻴﺖ ﺑﻬﺒﻮد وﺿﻌﻴﺖ ﺑﺤﺮاﻧﻲ ﺳﻠﻮلﻫﺎي ﻣﻔﺎﺻﻞ ﻣﺎﻧﻨﺪ ﻛﻨﺪروﺳـﻴﺖﻫـﺎ
ﻛﻪ ﺑﺎ ﮔﺮاﻓﻲ Three joint viewﺗﺄﻳﻴﺪ ﺷﺪه ﺑﻮد ،وﺟﻮد درد رادﻳﻮﻛـﻮﻻر
)ﺗﻮﻟﻴﺪ ﺳـﻠﻮلﻫـﺎي ﻏـﻀﺮوﻓﻲ( ،اوﺳﺘﺌﻮﺳـﻴﺖﻫـﺎ )ﺗﻮﻟﻴـﺪ ﺳـﻠﻮلﻫـﺎي
زاﻧﻮ ،ﻣﺼﺮف داروﻫﺎي ﺿﺪ اﻧﻌﻘـﺎدي ،آرﺗـﺮوز ﭘـﺲ از ﺗﺮوﻣـﺎ ،ﺗﺰرﻳـﻖ
اﺳﺘﺨﻮاﻧﻲ( و ﻓﻴﺒﺮوﺑﻼﺳﺖﻫﺎ )ﺗﻮﻟﻴﺪ ﺳﻠﻮلﻫﺎي ﺗﺎﻧﺪون ،ﻟﻴﮕﺎﻣﺎن و دﻳﮕﺮ
اﻳﻨﺘﺮاآرﺗﻴﻜﻮﻻر ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ﻃﻲ 12ﻣﺎه ﮔﺬﺷﺘﻪ از ﻣﻄﺎﻟﻌـﻪ ﺧـﺎرج
ﺑﺎﻓــﺖﻫــﺎي ﻧــﺮم( ﻣــﻲﺑﺎﺷــﺪ .در ﻣﻄﺎﻟﻌــﻪ Reevesﮔــﺰارش ﻛــﺮد ﻛــﻪ
ﺷﺪﻧﺪ .ﻻزم ﺑﻪ ذﻛﺮ اﺳﺖ ﻛﻪ در اﻳﻦ ﺑﻴﻤـﺎران ﺗـﺸﺨﻴﺺ اﺳـﺘﺌﻮآرﺗﺮﻳﺖ
ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﺎ دﻛـﺴﺘﺮوز %10ﺑـﻪﻃـﻮر ﻣﻌﻨـﻲداري ﻧـﺴﺒﺖ ﺑـﻪ ﭘﻼﺳـﺒﻮ
زاﻧﻮ ﺑﺮاﺳﺎس ﻳﺎﻓﺘﻪﻫـﺎي رادﻳـﻮﮔﺮاﻓﻲ ﻣﻄـﺎﺑﻖ ﺑـﺎ ﻛﺮاﻳﺘﺮﻳـﺎي
Kellgren-
ﻣﻮﺟﺐ ﺑﻬﺒﻮد درد و ﻋﻼﻳﻢ ﺑﺎﻟﻴﻨﻲ ﺑﻴﻤﺎر ﻣـﻲﺷـﻮد 24.ﺗـﺎﻛﻨﻮن ﻣﻄﺎﻟﻌـﺎت
lawrenceداده ﺷﺪ 26.ﺳﭙﺲ ﺑﻴﻤﺎران ﺑﺮ اﺳﺎس ﺟﺪول اﻋﺪاد ﺗﺼﺎدﻓﻲ ﺑﻪ
ﻣﺨﺘﻠﻔﻲ در ﻣﻮرد اﺛﺮات درﻣﺎﻧﻲ دﻛﺴﺘﺮوز ﭘﺮوﻟـﻮﺗﺮاﭘﻲ ﺑـﺎ ﻏﻠﻈـﺖﻫـﺎي
دو ﮔﺮوه 50ﻧﻔﺮي ﺗﺰرﻳﻖ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ )ﮔﺮوه اول( و ﭘﺮوﻟـﻮﺗﺮاﭘﻲ
ﻣﺨﺘﻠﻒ در درﻣﺎن اﺳﺘﺌﻮآرﺗﺮﻳﺖ ﺻﻮرت ﮔﺮﻓﺘﻪ اﺳﺖ وﻟﻲ ﻫﻨﻮز اﺛـﺮات
ﺑﺎ دﻛﺴﺘﺮوز ) %25ﮔﺮوه دوم( ﺗﻘﺴﻴﻢ ﺷﺪﻧﺪ .ﺳﭙﺲ ﺑﻴﻤـﺎر در وﺿـﻌﻴﺖ
درﻣﺎﻧﻲ آن ﻧﺎﻣﺸﺨﺺ ﻣﺎﻧﺪه و ﺑﻪ آن ﭘﺎﺳﺦ داده ﻧﺸﺪه اﺳﺖ .ﺑﺎ ﺗﻮﺟﻪ ﺑـﻪ
ﺳﻮﭘﺎﻳﻦ ﻗﺮار داده ﺷﺪ ،ﺑﺎ ﻓﻠﻜﺴﻴﻮن زاﻧـﻮ ﺑـﻪ اﻧـﺪازه 10-15درﺟـﻪ در
ﻧﻈﺮات ﻣﺘﻨﺎﻗﺾ و ﻣﻄﺎﻟﻌﺎت ﺑﺴﻴﺎر ﻣﺤﺪودي ﻛﻪ در ﻣﻮرد ﺗـﺎﺛﻴﺮ درﻣـﺎﻧﻲ
ﺳﻤﺖ ﻣﺪﻳﺎل زاﻧﻮ ﻟﻨﺪﻣﺎرك ﻧﺎﺣﻴﻪ ﺗﺰرﻳﻖ ﻣـﺸﺨﺺ ﺷـﺪ .ﺳـﭙﺲ ﻣﺤـﻞ
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﺮاي درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ اﻧﺠﺎم ﺷـﺪه و
ﺗﺰرﻳﻖ ﺑﺎ ﻣﺤﻠﻮل ﭘﻮوﻳﺪون آﻳﻮدﻳﻦ ﺿﺪﻋﻔﻮﻧﻲ و ﺑﺎ ﺗﺰرﻳﻖ ﻳﻚ ﻣﻴﻠﻲﻟﻴﺘـﺮ
اﻳﻦﻛﻪ ﺗﺎﻛﻨﻮن ﻣﻄﺎﻟﻌﻪاي در ﻣﻮرد دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑـﺎ ﻏﻠﻈـﺖ %25
ﻣﺤﻠﻮل ﻟﻴﺪوﻛﺎﻳﻴﻦ %2ﻧﺎﺣﻴﻪ ﺗﺰرﻳﻖ ﺑﻲﺣﺲ ﺷﺪ و ﺑﺎ اﺳﺘﻔﺎده از ﺳـﻮزن
و ﻣﻘﺎﻳﺴﻪ آن ﺑﺎ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ﺑﺮاي درﻣﺎن درد اﺳـﺘﺌﻮآرﺗﺮﻳﺖ زاﻧـﻮ
ﺷﻤﺎره 27ﭘﺲ از آﺳﭙﻴﺮاﺳﻴﻮن و اﻃﻤﻴﻨﺎن از ﻗﺮارﮔﻴﺮي ﺻﺤﻴﺢ ﺳـﻮزن،
اﻧﺠﺎم ﻧﺸﺪه اﺳﺖ ،ﻟﺬا ﭘﻴﺸﻨﻬﺎد ﮔﺮدﻳﺪ ﺑﺎ ﻃﺮاﺣـﻲ اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ ،اﺛـﺮات
داﺧــﻞ ﻣﻔــﺼﻞ ﺗﺰرﻳــﻖ اﻧﺠــﺎم ﺷــﺪ .ﮔــﺮوه اول دو ﻣﻴﻠــﻲﻟﻴﺘــﺮ ﻣﺤﻠــﻮل
ﻛﻮﺗﺎهﻣﺪت ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧﻞ ﻣﻔﺼﻠﻲ در
ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ )ﺳـﻴﻨﻮﻛﺮوم ،%1ﺷـﺮﻛﺖ ﺳـﺎزﻧﺪه ،CROMAﻛـﺸﻮر
ﺑﻬﺒــﻮد درد و ﻋﻤﻠﻜــﺮد زاﻧــﻮ و ﻛﻴﻔﻴــﺖ زﻧــﺪﮔﻲ در ﺑﻴﻤــﺎران ﻣﺒــﺘﻼ ﺑــﻪ
اﺗﺮﻳﺶ( ،ﭘﻨﺞ ﺗﺰرﻳﻖ ﺑﻪ ﻓﻮاﺻﻞ ﻳـﻚ ﻫﻔﺘـﻪ و ﮔـﺮوه دوم دو ﻣﻴﻠـﻲﻟﻴﺘـﺮ
اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ارزﻳﺎﺑﻲ و ﻣﻘﺎﻳﺴﻪ ﺷﻮد.
دﻛﺴﺘﺮوز ،%25ﺳﻪ ﺗﺰرﻳﻖ ﺑﻪ ﻓﻮاﺻﻞ ﻳﻚﻣﺎه درﻳﺎﻓﺖ ﻛﺮدﻧﺪ .ﭘـﻨﺞ آﻳـﺘﻢ
ﻫﻴﭙﺮﺗﻮﻧﻴﻚ ﻃﻲ ﭼﻨﺪ ﺛﺎﻧﻴﻪ ﺗﺎ ﭼﻨﺪ دﻗﻴﻘﻪ ﻣﻨﺠﺮ ﺑﻪ اﻓـﺰاﻳﺶ ﺳـﻄﺢ
ﺷﺎﻣﻞ درد ،ﻋﻼﻳﻢ ﺧﺸﻜﻲ زاﻧﻮ ،ﻓﻌﺎﻟﻴﺖﻫﺎي روزاﻧﻪ ،ﻋﻤﻠﻜﺮد ورزﺷﻲ و
روش ﺑﺮرﺳﻲ
ﺗﻔﺮﻳﺤﻲ و ﻛﻴﻔﻴﺖ زﻧﺪﮔﻲ ﻣﺮﺗﺒﻂ ﺑﺎ زاﻧﻮ ﺑﺮ اﺳـﺎس ﭘﺮﺳـﺶﻧﺎﻣـﻪ
Knee
) 27injury and Osteoarthritis Outcome Score (KOOSدر دو ﻧﻮﺑـﺖ،
ﭘﺲ از اﺧﺬ ﺗﺎﻳﻴﺪﻳﻪ ﻛﻤﻴﺘﻪ اﺧﻼق و ﭘﮋوﻫﺶ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ
ﻗﺒﻞ از ﺷﺮوع درﻣﺎن و ﺳﻪ ﻣـﺎه ﭘـﺲ از آﺧـﺮﻳﻦ ﺗﺰرﻳـﻖ ﺗﻮﺳـﻂ ﺑﻴﻤـﺎر
ﺷﻬﻴﺪﺑﻬﺸﺘﻲ ،در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻛﻪ ﺑﻪ ﺻﻮرت ﻛﺎرآزﻣﺎﻳﻲ ﺑﺎﻟﻴﻨﻲ دوﺳـﻮﻛﻮر
ﺗﻜﻤﻴﻞ ﺷﺪ .ﺳﭙﺲ اﻃﻼﻋﺎت دﻣﻮﮔﺮاﻓﻴﻚ و ﻧﺘﺎﻳﺞ ﺣﺎﺻﻠﻪ از ﭘﺮﺳﺶﻧﺎﻣﻪ
ﺗﺼﺎدﻓﻲ ﺷﺪه اﻧﺠﺎم ﺷﺪ ،از ﺑﻴﻦ ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ ﺑـﻪ اﺳـﺘﺌﻮآرﺗﺮﻳﺖ زاﻧـﻮ
KOOSدر ﺑﺮﮔﻪﻫﺎي اﻃﻼﻋﺎﺗﻲ از ﭘﻴﺶ آﻣـﺎده ﺷـﺪه ﺛﺒـﺖ ﺷـﺪﻧﺪ .ﻛﻠﻴـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻘﺎﻳﺴﻪ ﺗﺎﺛﻴﺮ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧﻞ ﻣﻔﺼﻠﻲ در درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ
121
اﻃﻼﻋﺎت ﻛﺪﮔﺬاري ﺷﺪه ،ﺗﻮﺳﻂ ﺑﺮﻧﺎﻣﻪ آﻣﺎري SPSSوﻳﺮاﺳﺖ 16وارد
40-70ﺳﺎل ﺑﻮد .ﻣﻴـﺰان ﻛـﺎﻫﺶ درد دوازده ﻫﻔﺘـﻪ ﭘـﺲ از ﺗﺰرﻳـﻖ در
Kolmogorov-
ﮔــﺮوه دﻛــﺴﺘﺮوز ﭘﺮوﻟــﻮﺗﺮاﭘﻲ (P=0/0001) 24/2±11/05و در ﮔــﺮوه
Smirnovﻧﺮﻣــﺎل ﺑــﻮدن ﭘﺮاﻛﻨــﺪﮔﻲ ﻧﻤﻮﻧــﻪﻫــﺎ ﺑﺮرﺳــﻲ ﺷــﺪ و ﻣﻘﺎﻳــﺴﻪ
ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ (P=0/0001) 24/7±12/4ﺑـﻮد .ﻣﻘﺎﻳـﺴﻪ ﺷـﺪت درد
Paired t- ،Student’s t-test
ﻗﺒﻞ از ﺗﺰرﻳﻖ و دوازده ﻫﻔﺘﻪ ﭘﺲ از ﺗﺰرﻳـﻖ ﺑـﻴﻦ ﮔـﺮوهﻫـﺎي ﻣﺨﺘﻠـﻒ
ﺣﺎﻓﻈﻪ راﻳﺎﻧﻪ ﮔﺮدﻳﺪﻧـﺪ .ﺳـﭙﺲ ﺑـﺎ اﺳـﺘﻔﺎده از آزﻣـﻮن ﻣﺘﻐﻴﺮﻫﺎي ﻛﻤﻲ ﺑﻴﻦ ﮔﺮوهﻫﺎ ﺗﻮﺳﻂ آزﻣـﻮن
2
Mann-Whitney ،testو ﻣﺘﻐﻴﺮﻫﺎي ﻛﻴﻔـﻲ ﺗﻮﺳـﻂ آزﻣـﻮن ﻣﺤﺎﺳـﺒﻪ
ﺑﻴﻤﺎران از ﻧﻈـﺮ آﻣـﺎري ﺗﻔـﺎوت ﻣﻌﻨـﻲداري را ﻧـﺸﺎن ﻧـﺪاد ).(P>0/05
ﮔﺮدﻳﺪ .ﻫﻢﭼﻨﻴﻦ از ﻧﻈﺮ آﻣﺎري P<0/05ﻣﻌﻨﻲدار در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪ.
ﺗﻐﻴﻴﺮات ﻛﺎﻫﺶ درد ﭘﺲ از درﻣﺎن ﺑﻴﻦ دو ﮔﺮوه ﺗﻔـﺎوت ﻣﻌﻨـﻲداري را ﻧﺸﺎن ﻧﺪاد ).(P=0/880 ﻣﻘﺎﻳﺴﻪ اﻃﻼﻋﺎت دﻣﻮﮔﺮاﻓﻴﻚ ﺑﻴﻤﺎران ﺑﻴﻦ دو ﮔـﺮوه ﻣـﻮرد ﺑﺮرﺳـﻲ در
ﻳﺎﻓﺘﻪﻫﺎ
ﺟﺪول 1آﻣﺪه اﺳﺖ .ﻣﻘﺎﻳﺴﻪ اﺳﻜﻮرﻫﺎي ﻗﺒـﻞ و ﭘـﺲ از درﻣـﺎن در دو ﻣﻴﺎﻧﮕﻴﻦ ﺳﻦ اﻓﺮاد ﻣﻮرد ﺑﺮرﺳﻲ 60/6±8/2ﺳﺎل در ﻣﺤـﺪوده ﺳﻨﻲ
ﮔﺮوه ﺑﻴﻤﺎران در ﺟﺪول 2آﻣﺪه اﺳﺖ.
ﺟﺪول :1 -ﻣﻘﺎﻳﺴﻪ اﻃﻼﻋﺎت دﻣﻮﮔﺮاﻓﻴﻚ ﺑﻴﻤﺎران ﺑﻴﻦ دو ﮔﺮوه ﻣﻮرد ﺑﺮرﺳﻲ *P
ﻣﺠﻤﻮع
ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ) 50زاﻧﻮ(
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ 50) %25زاﻧﻮ(
ﺳﻦ )ﺳﺎل(
60/6±8/2
60/1±8/3
60/1±8/2
0/650
(kg/m2) BMI
25/5±2/2
25/8±2/2
25/2±2/2
0/320
ﺟﻨﺲ :ﻣﺮد
)38(%37/3
)18(%36
)20(%38/5
زن
)63(%62/7
)32(%64
)30(%61/5
ﺷﻐﻞ :آزاد
)30(%29/4
)16(%32
)14(%26/9
ﺧﺎﻧﻪدار
)26(%52/9
)28(%56
)24(%50
ﺑﺎزﻧﺸﺴﺘﻪ
)9(%17/6
)6(%12
)12(%23/1
0/856
0/581
* آزﻣﻮن آﻣﺎري ،t- test :ﻣﻘﺎدﻳﺮ ﻣﻌﻨﻲدار .P<0/05
ﺟﺪول :2 -ﻣﻘﺎﻳﺴﻪ اﺳﻜﻮرﻫﺎي ﻗﺒﻞ و ﭘﺲ از درﻣﺎن ﺑﻴﻦ دو ﮔﺮوه ﻣﻮرد ﺑﺮرﺳﻲ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ) 50زاﻧﻮ(
1
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ 50) %25زاﻧﻮ( 1
2
3
4
ﻗﺒﻞ
ﺑﻌﺪ
ﻗﺒﻞ
ﺑﻌﺪ
P
P
P
P
ﻧﻤﺮه درد
45/1±19/8
69/8±10/2
44/6±16/8
68/8±11/4
0/880
0/644
<0/001
0/816
ﻧﻤﺮه ﻋﻼﻳﻢ ﺧﺸﻜﻲ زاﻧﻮ
46/4±10/4
56/1±8/3
44/8±9/4
54/9±8/9
0/462
0/459
<0/001
0/595
ﻧﻤﺮه ﻓﻌﺎﻟﻴﺖﻫﺎي روزاﻧﻪ
44/2±17/9
70±11
43/2±16/2
71/5±12/7
0/757
0/538
<0/001
0/573
ﻧﻤﺮه ﻋﻤﻠﻜﺮد ورزﺷﻲ و ﺗﻔﺮﻳﺤﻲ
24/4±21/8
48/4±15/2
13/7±15/5
42/5±13/4
0/038
0/042
<0/001
0/063
ﻧﻤﺮه ﻛﻴﻔﻴﺖ زﻧﺪﮔﻲ ﻣﺮﺗﺒﻂ ﺑﻪ زاﻧﻮ
26/3±17/8
41/3±11/2
25±17/6
38/8±14/6
0/802
0/338
<0/001
0/184
2
:Pﻣﻘﺎﻳﺴﻪ ﻗﺒﻞ از درﻣﺎن ﺑﻴﻦ دو ﮔﺮوه :P ،ﻣﻘﺎﻳﺴﻪ ﺑﻌﺪ از درﻣﺎن ﺑﻴﻦ دو ﮔﺮوه،
3 :P
ﻣﻘﺎﻳﺴﻪ ﻗﺒﻞ و ﭘﺲ از درﻣﺎن در ﻫﺮ ﮔﺮوه،
4 :P
ﺗﻐﻴﻴﺮات ﭘﺲ از درﻣﺎن ﻧﺴﺒﺖ ﺑﻪ ﻣﻴﺰان ﭘﺎﻳﻪ ﺑﻴﻦ دو ﮔﺮوه
* آزﻣﻮن آﻣﺎري Mann-Whitney :ﻣﻘﺎدﻳﺮ ﻣﻌﻨﻲدار .P<0/05
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
122
ﺳﻴﺪ ﻣﺴﻌﻮد ﻫﺎﺷﻤﻲ و ﻫﻤﻜﺎران
ﻗﺎﺑﻞ ﺗﻮﺟﻪ ﺷﻠﻲ ﻟﻴﮕﺎﻣﺎنﻫﺎي زاﻧﻮ ﻣﻲﺷﻮد 35.در ﻣﻄﺎﻟﻌﻪ دﻳﮕـﺮي ﺑـﺮاي
ﺑﺤﺚ
درﻣﺎن اﺳﺘﺌﻮآرﺗﺮﻳﺖ ﻣﻔﺎﺻﻞ اﻧﮕﺸﺖ از دﻛـﺴﺘﺮوز %10ﺑـﻪ ﻓﻮاﺻـﻞ دو اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ﻳﻜﻲ از ﻋﻠﻞ اﺻﻠﻲ ﺑﻴﻤـﺎريﻫـﺎي ﻧـﺎﺗﻮانﻛﻨﻨـﺪه
ﻣﺎه اﺳﺘﻔﺎده ﻛﺮدﻧﺪ ﻛﻪ ﺑﺎ اﺛﺮات ﺳﻮدﻣﻨﺪ درﻣﺎﻧﻲ ﻫﻤﺮاه ﺑﻮد 24.در ﻣﻄﺎﻟﻌـﻪ
ﻣﻲﺑﺎﺷﺪ ﻛﻪ درﻣﺎن ﺟﺮاﺣﻲ آن ﺑﺎ ﻧﺘﺎﻳﺞ ﻣﻄﻠـﻮﺑﻲ ﻫﻤـﺮاه اﺳـﺖ وﻟـﻲ ﺑـﺎ
دﻳﮕﺮي ﮔﺰارش ﻛﺮدﻧﺪ در ﻛـﺸﻮرﻫﺎي ﺟﻬـﺎن ﺳـﻮم ﻛـﻪ اﻧﺠـﺎم اﻋﻤـﺎل
ﺗﻮﺟﻪ ﺑﻪ ﺧﻄﺮات ﺟﺮاﺣﻲ ﻧﻤﻲﺗﻮان در ﺗﻤﺎم ﻣﻮارد اﺳﺘﺌﻮآرﺗﺮﻳﺖ اﻗـﺪام
ﺟﺮاﺣﻲ ﻛﺎرﮔﺬاري زاﻧﻮ ﻗﺎﺑﻞ دﺳﺘﺮﺳﻲ ﻧﻴﺴﺖ ،ﺑـﺮ ﺧـﻼف ﻋﻼﻣـﺖدار
ﺑﻪ ﺟﺮاﺣﻲ ﻧﻤﻮد .ﻋﻼوه ﺑﺮ آن ﻫﻴﭻﻳﻚ از ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ اﺳﺘﺌﻮآرﺗﺮﻳﺖ
ﺑﻮدن ﺑﻴﻤﺎران ،ورزش ،ﻓﻴﺰﻳﻮﺗﺮاﭘﻲ ﻳـﺎ NSAIDsﺗﺠـﻮﻳﺰ ﻣـﻲﺷـﻮد .اﻳـﻦ
ﺗﻤﺎﻳﻞ ﺑﻪ اﻧﺠﺎم ﺟﺮاﺣﻲ ﻧﺪارﻧﺪ 28.ﺑﻨﺎﺑﺮاﻳﻦ ﺗﺸﺨﻴﺺ زودرس ﺑﻴﻤﺎري و
ﭘﮋوﻫﺶﮔﺮان ﻧﺸﺎن دادﻧﺪ دﻛﺴﺘﺮوز %10ﻣﻲﺗﻮاﻧﺪ ﺷﻠﻲ ﻟﻴﮕﺎﻣﺎن ACLرا
5و4
ﻛﻪ ﺑﺎ ﭘﺎرﮔﻲ ﻫﻤﺮاه ﻧﺒﺎﺷﺪ ،اﺻﻼح ﻛﻨﺪ و ﻫﻢﭼﻨﻴﻦ ﺳـﺒﺐ ﭘﻴـﺸﮕﻴﺮي از
اﻣﺮوزه از ﺗﺰرﻳﻖ داﺧﻞ ﻣﻔﺼﻠﻲ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ﺑـﻪﻃـﻮر وﺳـﻴﻌﻲ در
36
ﺷﻠﻲ ﺗﺪرﻳﺠﻲ ﭘﺲ از ﺟﺮاﺣﻲ در ﻣﻔﺎﺻﻞ ﺑﺎ ﭘﺘﺎﻧﺴﻴﻞ ﺟﺎﺑﻪﺟﺎﻳﻲ ﺷﻮد.
درﻣﺎن اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ اﺳﺘﻔﺎده ﻣﻲﺷﻮد 6-10.ﻣﻜﺎﻧﻴﺴﻢ اﺛﺮ ﻫﻴﺎﻟﻮروﻧﻴﻚ
اﺣﺘﻤﺎﻻ ﺗﺰرﻳﻖ ﻳﻚ ﻣﺤﻠﻮل ﻣﺤﺮك ﻣﺎﻧﻨﺪ دﻛـﺴﺘﺮوز ﺑـﻪ داﺧـﻞ ﻣﻔـﺼﻞ
اﺳﻴﺪ از ﻃﺮﻳﻖ اﻓﺰاﻳﺶ ﺗﻌﺪاد ﻛﻨﺪروﺳﻴﺖﻫﺎي زﻧﺪه ،اﻳﺠـﺎد ﺿـﺨﺎﻣﺖ و
آﺳــﻴﺐ دﻳــﺪه ،ﺑــﺎ واﻛــﻨﺶﻫــﺎي اﻟﺘﻬــﺎﺑﻲ ﻣﻮﺿــﻌﻲ ﻣﻮﺟــﺐ اﻓــﺰاﻳﺶ
ﺗﺮﻣﻴﻢ در ﺳﻄﺢ ﻏﻀﺮوف ،ﭘﻴﺸﮕﻴﺮي از ﺗﻮﻟﻴﺪ ﻧﻴﺘﺮﻳﻚ اﻛـﺴﺎﻳﺪ در ﻣـﺎﻳﻊ
ﺧﻮنرﺳﺎﻧﻲ در اﻃﺮاف ﻣﻔﺼﻞ و ﺑﺎﻓﺖ آﺳﻴﺐ دﻳﺪه ﻣـﻲﺷـﻮد و از اﻳـﻦ
Synoviaو ﻣﻴﻨﻴــﺴﻚ ،ﻣﻬــﺎر آﭘﭙﺘــﻮز ﻛﻨﺪروﺳــﻴﺖ ،ﻛــﺎﻫﺶ ﻣ ـﺎﺗﺮﻳﻜﺲ
ﻃﺮﻳﻖ ﺧﻮدﺑﻪﺧﻮد ﻣﻮﺟﺐ ﺗﺮﻣﻴﻢ در آن ﻧﺎﺣﻴﻪ ﻣﻲﺷﻮد .در ﻣﻄﺎﻟﻌﺎﺗﻲ ﻧﻴـﺰ
29-32
ﻧﺸﺎن دادﻧﺪ ﻛﻪ ﭘﺮوﻟﻮﺗﺮاﭘﻲ در ﻛﻨﺘﺮل درد و ﺑﺮﮔﺸﺖ آﺳﻴﺐ ﻣﻔﺼﻞ ﻣﻮﺛﺮ
ﻣﺪاﺧﻼت درﻣﺎﻧﻲ ﻧﮕﻪدارﻧﺪه در اﻳﻦ ﺑﻴﻤﺎران در اوﻟﻮﻳـﺖ ﻣـﻲﺑﺎﺷـﺪ.
ﻣﺘﺎﻟﻮﭘﺮوﺗﺌﻴﻨﺎز 3 -و اﻳﻨﺘﺮﻟﻮﻛﻴﻦ 1 -ﺑﺘﺎ در ﻣﺎﻳﻊ Synoviaﻣﻲﺑﺎﺷـﺪ.
37
ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ ﺟﺰﻳﻲ از ﺗﺮﻛﻴـﺐ ﻃﺒﻴﻌـﻲ ﻏـﻀﺮوف اﺳـﺖ و ﻧﻘـﺶ
اﺳﺖ .ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻳﺎﻓﺘـﻪﻫـﺎي ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ ،اﺳـﺘﻔﺎده از دﻛـﺴﺘﺮوز
ﻣﻬﻤﻲ در ﺧﺎﺻﻴﺖ وﻳﺴﻜﻮاﻻﺳﺘﻴﺴﻴﺘﻪ ﻣﺎﻳﻊ ﺳﻴﻨﻮوﻳﺎل دارد .ﻫﻴﺎﻟﻮروﻧﻴﻚ
ﭘﺮوﻟﻮﺗﺮاﭘﻲ روﺷﻲ ﺳﺎده ،اﻳﻤـﻦ ،ارزان ،در دﺳـﺘﺮس و ﺑـﺪون ﻋﺎرﺿـﻪ
اﺳﻴﺪ ﻟﻮﺑﺮﻳﻜﺎﻧﺖ ﻣﻔﺼﻞ و ﻓﺎﻛﺘﻮر ﻓﻴﺰﻳﻮﻟﻮژﻳﻚ رﺷﺪ ﻏﻀﺮوف ﻣﻲﺑﺎﺷﺪ.
ﻧﺴﺒﺖ ﺑﻪ درﻣﺎنﻫﺎي دﻳﮕﺮ در اﻳﻦ ﺑﻴﻤﺎران ﻣﻲﺑﺎﺷـﺪ ﻛـﻪ ﺗﻮﺳـﻂ دﻳﮕـﺮ
در ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ ،در ﻫــﺮ ﻳـﻚ از ﮔـﺮوهﻫــﺎي ﻫﻴﺎﻟﻮروﻧﻴـﻚ اﺳــﻴﺪ و
38-41
ﻣﻄﺎﻟﻌﺎت ﻧﻴﺰ ﺗﺎﻳﻴﺪ ﺷﺪه اﺳﺖ.
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ درد زاﻧـﻮ ﻛـﺎﻫﺶ ﻣﻌﻨـﻲداري را ﻧـﺸﺎن داد وﻟـﻲ
در ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﻣﺮوري ﺗﻮﺳﻂ Uthmanﻧﻴﺰ ﻛﻪ درﻣﺎنﻫﺎي ﻣﺨﺘﻠـﻒ
ﻣﻘﺎﻳــﺴﻪ ﻧﺘــﺎﻳﺞ درﻣــﺎﻧﻲ در دو ﮔــﺮوه درﻣــﺎﻧﻲ ﻫﻴﺎﻟﻮروﻧﻴــﻚ اﺳــﻴﺪ و
اﻳﻨﺘﺮاآرﺗﻴﻜﻮﻻر ﺑﺮاي اﺳﺘﺌﻮآرﺗﺮﻳﺖ را در ﺳﺎلﻫﺎي 1968-2002ﺑﺮرﺳﻲ
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ از ﻧﻈﺮ آﻣﺎري ﺗﻔﺎوت ﻣﻌﻨـﻲداري را ﻧـﺸﺎن ﻧـﺪاد.
ﻛﺮده ﺑﻮد ،ﮔﺰارش ﻛـﺮد دﻛـﺴﺘﺮوز ﭘﺮوﻟـﻮﺗﺮاﭘﻲ داراي ﻗﺎﺑﻠﻴـﺖ درﻣـﺎن
ﺑﺮاﺳﺎس ﻧﺘﺎﻳﺞ دﻳﮕﺮ ﻣﻄﺎﻟﻌﺎت اﻧﺠﺎم ﺷﺪه ،اﻓﺰاﻳﺶ ﮔﻠﻮﻛﺰ ﺧﺎرج ﺳﻠﻮﻟﻲ
آرﺗﺮﻳﺖ ﻣﻔﺎﺻﻞ ﻣـﻲﺑﺎﺷـﺪ 42.در ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ ﻧـﺸﺎن داده ﺷـﺪ ﻛـﻪ
ﺣﺘﻲ ﺑﻪ ﻣﻴﺰان %5ﻣﻮﺟﺐ اﻓـﺰاﻳﺶ ﻣﻴـﺰان ،IGF-2 ،IGF-1در ﻣﺰاﻧـﺸﻴﺎل
دﻛﺴﺘﺮوز ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﻪ اﻧﺪازه ﺗﺰرﻳﻖ داﺧﻞ ﻣﻔﺼﻠﻲ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳـﻴﺪ
ﺳﻠﻮلﻫﺎي اﻧﺴﺎﻧﻲ TGF-β1 20،در ﺳﻠﻮلﻫﺎي ﺗـﻚﻫـﺴﺘﻪاي اﻧـﺴﺎﻧﻲ 21و
در درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ﻣﻮﺛﺮ اﺳﺖ .ﻟﺬا در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﻪ دﻟﻴﻞ
ﻣﺰاﻧﺸﻴﺎل اﻧﺴﺎﻧﻲ20،و) PDGF-β 17ﭘﻼﻛﺖ ﻣﺸﺘﻖ ﺷﺪه از ﻓﺎﻛﺘﻮر رﺷﺪ ،(β
اﻳﻤﻨﻲ ،ﻧﺘﺎﻳﺞ درﻣﺎن ،ارزان ﺑﻮدن دﻛﺴﺘﺮوز ،ﻛـﻢﺗـﺮ ﺗﻬـﺎﺟﻤﻲ ﺑـﻮدن ﻳـﺎ
33
ﺗﻌــﺪاد ﻛــﻢﺗــﺮ دﻓﻌــﺎت ﺗﺰرﻳــﻖ و ﭘــﺬﻳﺮش راﺣــﺖ آن ﺗﻮﺳــﻂ ﺑﻴﻤــﺎر،
bFGFدر ﻓﻴﺒﺮوﺑﻼﺳﺖﻫﺎي ﻟﺜﻪاي اﻧﺴﺎﻧﻲ CTGF 19،ﻓﺎﻛﺘﻮر رﺷـﺪ ﺑﺎﻓـﺖ
ﭘﺮوﻟـﻮﺗﺮاﭘﻲ ﺑـﺎ دﻛـﺴﺘﺮوز %25در درﻣـﺎن درد اﺳـﺘﺌﻮآرﺗﺮﻳﺖ زاﻧـﻮ در
ﻧﺮم در ﺳـﻠﻮلﻫـﺎي ﻣﺰاﻧـﺸﻴﺎل اﻧـﺴﺎن 18،ﻣـﻲﺷـﻮد .ﻫـﻢﭼﻨـﻴﻦ ﮔﻠـﻮﻛﺰ
ﻛﻮﺗﺎهﻣﺪت درﻣـﺎﻧﻲ ﻣـﻮﺛﺮ و اﻳﻤـﻦ ﺷـﻨﺎﺧﺘﻪ ﺷـﺪه اﺳـﺖ .ﺑﻨـﺎﺑﺮاﻳﻦ ﺑـﻪ
ﺳﻠﻮلﻫﺎي ﻣﻨﻮﻧﻮﻛﻠﺌﺎر ﺧﻮﻧﻲ ﭘﺘﺎﻧﺴﻴﻞ ﻓﺎﻛﺘﻮرﻫﺎي ﻣﺨﺮب )اﻳﻨﺘﺮﻟﻮﻛﻴﻦﻫـﺎ
ﻣﺘﺨﺼﺼﻴﻦ درد ﭘﻴﺸﻨﻬﺎد ﻣﻲﮔﺮدد ﻛﻪ در درﻣﺎن درد ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ ﺑـﻪ
ﻣﺎﻧﻨﺪ (IL-10 ،IL-6 ،IL-2را ﺳﺎﭘﺮس ﻣﻲﻛﻨﺪ 21.از ﻃﺮﻓﻲ ﭘﺎﺳـﺦ ﺳـﻠﻮﻟﻲ
اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮ ﭘﺮوﻟﻮﺗﺮاﭘﻲ ﺑﺎ دﻛـﺴﺘﺮوز %25را در ﺳـﻪ ﺗﺰرﻳـﻖ ﺑـﻪ
ﺑﻪ اﻓﺰاﻳﺶ ﮔﻠﻮﻛﺰ ﺧﺎرج ﺳﻠﻮﻟﻲ ﺳﺮﻳﻊ ﻣﻲﺑﺎﺷﺪ و ﻣﻴﺰان DNAﻣﺮﺑﻮط ﺑﻪ
ﻓﻮاﺻﻞ ﻳﻚﻣﺎه در ﻧﻈﺮ داﺷﺘﻪ ﺑﺎﺷﻨﺪ .ﭘﻴﺸﻨﻬﺎد ﻣﻲﮔـﺮدد اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ ﺑـﺎ
ﺗﻮﻟﻴﺪ ﻓﺎﻛﺘﻮر رﺷﺪ در اﺛﺮ ﺗﻤﺎس ﺳﻠﻮﻟﻲ ﺑﺎ اﻓﺰاﻳﺶ ﮔﻠـﻮﻛﺰ ﻧﻴـﺰ اﻓـﺰاﻳﺶ
ﺣﺠﻢ ﻧﻤﻮﻧﻪ ﺑﻴﺶﺗﺮ ﺑﺎ ﭘﻲﮔﻴﺮي ﻛﻮﺗﺎهﻣﺪت و ﺑﻠﻨﺪﻣﺪت و ﻏﻠﻈـﺖﻫـﺎي
ﻣﻲﻳﺎﺑﺪ 34.در ﻣﻄﺎﻟﻌﻪاي ﻧﻴﺰ ﮔﺰارش ﻛﺮدﻧﺪ اﺳـﺘﻔﺎده از ﻣﺤﻠـﻮل ﺗﺮﻛﻴﺒـﻲ
ﻣﺨﺘﻠﻒ دﻛﺴﺘﺮوز و دﻓﻌﻪﻫـﺎي ﻣﺨﺘﻠـﻒ ﭘﺮوﻟـﻮﺗﺮاﭘﻲ و ﻣﻘﺎﻳـﺴﻪ آن ﺑـﺎ
)ﻓﻨﻞ ،%1/25دﻛـﺴﺘﺮوز %12/5و ﮔﻠﻴـﺴﻴﺮﻳﻦ (%12/5ﻣﻮﺟـﺐ ﺑﻬﺒـﻮد
ﺳﻴﻨﻮﻛﺮوم ﻓﻮرت %2اﻧﺠﺎم ﺷﻮد.
در ﺳﻠﻮلﻫﺎي ﻣﺰاﻧﺸﻴﺎل اﻧﺴﺎﻧﻲ 17و ﺳﻠﻮلﻫـﺎي اﻧـﺪوﺗﻠﻴﺎل ﻛـﺎﭘﻴﻼري،
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
S.M. et دﻛﺴﺘﺮوز al. ﻣﻔﺼﻠﻲ در درﻣﺎن درد اﺳﺘﺌﻮآرﺗﺮﻳﺖ زاﻧﻮHashemi ﭘﺮوﻟﻮﺗﺮاﭘﻲ داﺧﻞ ﻣﻘﺎﻳﺴﻪ ﺗﺎﺛﻴﺮ ﻫﻴﺎﻟﻮروﻧﻴﻚ اﺳﻴﺪ و
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39. Dye SF. The future of anterior cruciate ligament restoration. Clin Orthop Relat Res 1996;(325):130-9. 40. Gerich TG, Kang R, Fu FH, Robbins PD, Evans CH. Gene transfer to the rabbit patellar tendon: potential for genetic enhancement of tendon and ligament healing. Gene Ther 1996;3(12):1089-93. 41. Pelletier JP, Caron JP, Evans C, Robbins PD, Georgescu HI, Jovanovic D, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 1997;40(6):1012-9. 42. Uthman I, Raynauld JP, Haraoui B. Intra-articular therapy in osteoarthritis. Postgrad Med J 2003;79(934):449-53.
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺗﺸﺨﻴﺺ روش ﭘﺎﻳﺶ ﻛﺎراﻳﻲ Tehran University Medical Journal; Vol. 70, No.ﺑﺮاي 2, May 2012:دو119-125
Intra-articular hyaluronic acid injections Vs. dextrose prolotherapy in the treatment of osteoarthritic knee pain ]
Abstract Seyed Masoud Hashemi M.D.1* Firooz Madadi M.D.2 Saied Razavi M.D.1 Mahshid Nikooseresht M.D.3 Farshad Hassanzadeh Kiyabi M.D.1 Somayyeh Nasiripour Ph.D.4 1- Department of Anesthesiology Akhtar Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2- Department of Orthopedic, Akhtar Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3- Department of Anesthesiology, Beasat Hospital, Hamedan University of Medical Sciences, Hamedan, Iran. 4- Pharm D., Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Received: September 13, 2011 Accepted: January 11, 2010
Background: Conservative treatment needs to be tried prior to surgical treatment of knee osteoarthritis. This study was designed to evaluate the short-term effects of dextrose prolotherapy on pain relief and functional improvement in knee osteoarthritis in comparison with intra-articular hyaluronic acid injections. Methods: In this double blind clinical trial, 100 patients, aged 40-70 years, with complaints of knee pain lasting >3 months were recruited in Akhtar hospital during the years 2010 to 2011. The patients met the criteria proposed by the American College of Rheumatology (ACR) for knee osteoarthritis. 50 patients in hyaluronic acid group received five 2 ml injections of hyaluronic acid (Synocrom Forte® 1%) weekly and 50 patients in dextrose prolotherapy group received three 2 ml bimonthly injections of 25% dextrose. The patients were evaluated before and after treatment in terms of pain and functionality using the Knee injury and Osteoarthritis Outcome Score (KOOS) selfquestionnaire. The patients were followed up for 12 weeks and were examined 12 weeks after the injections by an observer unaware of group assignments. The data were recorded for statistical analysis. Results: The mean age of the patients was 60.68.2 years. No significant differences were found between the two groups with respect to pre- and post-treatment KOOS scores. The scores showed significant improvements in all items following treatment in both groups (P<0.001). Conclusion: It seems that intra-articular injections of 25% dextrose prolotherapy could be as effective as hyaluronic acid injections for the treatment of knee pain due to OA. Keywords: Dextrose prolotherapy, hyaluronic acid, knee osteoarthritis.
*
Corresponding author: Akhtar Hospital, Elahiyeh St., Tehran, 1964714953, Islamic Republic of Iran. Tel: +98- 21- 22612252 E-mail: dr.hashemi@sbmu.ac.ir
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
ﻛﻠﻴﻪ ،اردﻳﺒﻬﺸﺖ 126-129 ،1391 ﺷﻤﺎره 2 ﻧﺎرﺳﺎ70 در دوره ﺗﻬﺮان، ﻋﻠﻮمﭘﻠﻲﭘﺰﺷﻜﻲ داﻧﺸﮕﺎه ﭘﺰﺷﻜﻲ، آﻧﺘﻲﺑﺎديﻣﺠﻠﻪ ﻳﻲ، ،ﻣﺰﻣﻦ ﺳﺎﻛﺎرﻳﺪي واﻛﺴﻦ ﺗﺰرﻳﻖ داﻧﺸﻜﺪه ﺑﻌﺪ از اﺧﺘﺼﺎﺻﻲ
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ﺑﺮرﺳﻲ ﻓﺮاواﻧﻲ ﭘﻮﻟﻴﭗﻫﺎ و ﺑﺪﺧﻴﻤﻲﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل در زﻧﺎن ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان و اﻧﺪوﻣﺘﺮ در ﺳﺎل 1389-90در ﺑﻴﻤﺎرﺳﺘﺎن ﻓﻴﺮوزﮔﺮ ،اﻛﺒﺮآﺑﺎدي و رﺳﻮل اﻛﺮم :ﮔﺰارش ﻛﻮﺗﺎه
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/10/19 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/09 :
ﺳﻴﻤﺎ ﺟﻌﻔﺮي *1،ﺳﻴﺎﻣﻚ ﺧﺎﻟﻘﻲ،
2
ﭼﻜﻴﺪه
4
ﻋﻠﻲ ﺑﺎﺳﻲ 3،ﻃﻴﺐ رﻣﻴﻢ
زﻣﻴﻨﻪ و ﻫﺪف :آدﻧﻮﻛﺎرﺳﻴﻨﻮم ﻛﻮﻟﻮن ﺑﻪ وﻳﮋه اﻧﻮاع ﺛﺎﻧﻮﻳﻪ ﺑﻪ ﺳﺮﻃﺎنﻫﺎي ﺗﺨﻤﺪان اﻏﻠﺐ در ﺗـﺸﺨﻴﺺﻫـﺎ ﻧﺎدﻳـﺪه ﮔﺮﻓﺘـﻪ
ﻣﻲﺷﻮﻧﺪ .ﻫﺪف از اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺮرﺳﻲ ﻫﻤﺮاﻫﻲ ﭘﻮﻟﻴﭗﻫﺎي ﻛﻮﻟﻮن ﺑﺎ ﺳﺮﻃﺎنﻫـﺎي ﺗﺨﻤـﺪان ﻣـﻲﺑﺎﺷـﺪ .روش ﺑﺮرﺳـﻲ:
-1ﮔﺮوه داﺧﻠﻲ -2ﮔﺮوه ﮔﻮارش
ﺑﻴﻤﺎران ﺑﻴﻤﺎرﺳﺘﺎنﻫﺎي ﻓﻴﺮوزﮔﺮ ،اﻛﺒﺮآﺑﺎدي و رﺳﻮل اﻛﺮم از ﺳﺎل 1389ﺗﺎ 1390ﺑﺎ ﺗﺸﺨﻴﺺ ﺳﺮﻃﺎن ﺗﺨﻤﺪان و اﻧﺪوﻣﺘﺮ
-3ﮔﺮوه ﺧﻮن و اﻧﻜﻮﻟﻮژي -4ﭘﮋوﻫﺸﮕﺮ ،ﻋﻀﻮ ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﺗﺮوﻣﺎ و
ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺘﻨﺪ .ﭘﻮﻟﻴﭗﻫﺎ و ﺗﻮﻣﻮرﻫﺎي ﻳﺎﻓﺖ ﺷﺪه در ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ ﺑﺎ روش اﻳﻤﻮﻧﻮﻫﻴﺴﺘﻮﺷﻴﻤﻲ از ﻧﻈﺮ اوﻟﻴﻪ ﻳﺎ ﻣﺘﺎﺳﺘﺎﺗﻴﻚ ﺑﻮدن ﺑﺮرﺳﻲ ﮔﺮدﻳﺪﻧﺪ .ﻳﺎﻓﺘﻪ ﻫﺎ 100 :ﺑﻴﻤﺎر ﺑﺎ ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 50/21ﺳﺎل ،ﻣﻴﺎﻧﮕﻴﻦ وزﻧﻲ 65/9ﻛﻴﻠـﻮﮔﺮم و
ﺟﺮاﺣﻲ ﺑﻴﻤﺎرﺳﺘﺎن ﺳﻴﻨﺎ
ﻣﻴﺎﻧﮕﻴﻦ 26/07kg/m2 ،BMIدر اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺷﺮﻛﺖ ﻛﺮدﻧﺪ .ﻓﺮاواﻧﻲ ﻛﻠﻲ ﭘﻮﻟﻴﭗﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل ﭘـﻨﺞ ﻣـﻮرد در 100ﻧﻔـﺮ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان. *
ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،ﻣﻴﺪان ﺗﻮﺣﻴﺪ ،ﺧﻴﺎﺑﺎن ﺳﺘﺎرﺧﺎن،
ﺧﻴﺎﺑﺎن ﻧﻴﺎﻳﺶ ،ﺑﻴﻤﺎرﺳﺘﺎن ﺣﻀﺮت رﺳﻮل اﻛﺮم
ﺑﻮد .اﻓﺮاد داراي ﺗﺸﺨﻴﺺ ﭘﻮﻟﻴﭗ ،ﺳﺎﺑﻘﻪ ﻓﺎﻣﻴﻠﻲ ﻣﺜﺒﺖ از ﻧﻈﺮ اﺑﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان داﺷﺘﻨﺪ .ﻧﺘﻴﺠﻪﮔﻴﺮي :ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ ﭘﺎﻳﻴﻦ ﺑﻮدن آﻣﺎر ﻣﺒﺘﻼﻳﺎن ﺑﻪ ﭘﻮﻟﻴﭗﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل ،ﭘﻲﮔﻴﺮي ﺑﻴﻤﺎران ﺟﻬﺖ اﻧﺠﺎم ﻏﺮﺑﺎﻟﮕﺮي ﺗﻮﺻﻴﻪ ﻧﻤﻲﺷﻮد.
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ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﭘﻮﻟﻴﭗ ﻛﻮﻟﻮرﻛﺘﺎل ،ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل ،ﺳﺮﻃﺎن ﺗﺨﻤﺪان ،ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ ،ﻏﺮﺑﺎﻟﮕﺮي.
از راهﻫﺎي ﺳﺎده و ﻛﻢ ﻫﺰﻳﻨﻪ ﺑﺮاي اﻃﻼع از زﻣﻴﻨـﻪﻫـﺎي ارﺛـﻲ اﺑـﺘﻼ ﺑـﻪ
ﻣﻘﺪﻣﻪ
ﺳﻨﺪرمﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل اﺳـﺖ .ﻣﻤﻜـﻦ اﺳـﺖ ﺳـﺎﺑﻘﻪ ﻓـﺎﻣﻴﻠﻲ دﻗﻴﻘـﻲ از
ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل دوﻣﻴﻦ ﻋﻠﺖ ﺷﺎﻳﻊ ﻣﺮگ و ﻣﻴﺮ ﻧﺎﺷﻲ از ﺳﺮﻃﺎن
ﻣﺒﺘﻼﻳﺎن ﺳﻨﺪرم ﻟﻴﻨﭻ ﺑﻪ دﻟﻴﻞ ﻛﻢ ﺑﻮدن ﺗﻌـﺪاد اﻋـﻀﺎي ﺧـﺎﻧﻮاده ،ﻋـﺪم
ﻣﻲﺑﺎﺷﺪ .اﻳﻦ ﺳـﺮﻃﺎن ﻣـﺴﻮول ﻣـﺮگ ﺳـﺎﻻﻧﻪ ﺣـﺪود 52000ﻧﻔـﺮ در
آﺷﻨﺎﻳﻲ ﭘﺰﺷﻜﺎن ﺑﺎ زﻣﻴﻨﻪﻫﺎي ارﺛﻲ اﻳﻦ ﺑﻴﻤﺎري و ﺗﻼش ﺟﻬﺖ ﺛﺒـﺖ آن
آﻣﺮﻳﻜﺎ و 146000ﻧﻔﺮ در اروﭘـﺎ ﺑـﻮده اﺳـﺖ 1-3.ﺣـﺪود 2-5درﺻـﺪ
7-9
و ﻣﺎﻧﻨﺪ آن وﺟـﻮد ﻧﺪاﺷـﺘﻪ ﺑﺎﺷـﺪ.
در ﺑﺮﺧـﻲ ﻣﺮاﻛـﺰ درﻣـﺎﻧﻲ ﺑـﺮاي
)(Lynch syndrome
ﺟﻠــﻮﮔﻴﺮي از ﻋــﻮارض ﻣﺘﺎﺳــﺘﺎﺗﻴﻚ اﻳـﻦ ﻧــﻮع ﺳــﺮﻃﺎنﻫــﺎ ﭘـﻲﮔﻴـﺮي
ﻫﺴﺘﻨﺪ ﻛﻪ ﻗﺒﻼً ﺗﺤـﺖ ﻋﻨـﻮان ﺳـﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘـﺎل ﻏﻴـﺮ ﭘـﻮﻟﻴﭙﻲ ارﺛـﻲ
ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ و اﻧﺠﺎم ﺑﺮﺧﻲ آزﻣﺎﻳﺸﺎت آﻧﺘﻲﺑـﺎدي اﻧﺠـﺎم ﻣـﻲﮔـﺮدد.
ﻣﻮارد ﺟﺪﻳـﺪ ﺗـﺸﺨﻴﺺ داده ﺷـﺪه ﺳـﻨﺪرم ﻟﻴـﻨﭻ )(HNPCC
Hereditary Nonpolyposis Colorectal Cancerﺷــﻨﺎﺧﺘﻪ
10-12
آدﻧﻮﻛﺎرﺳﻴﻨﻮﻣﺎي ﻛﻮﻟﻮن ﺷﺒﻴﻪ ﺑﻪ ﻛﺎرﺳﻴﻨﻮﻣﺎي اوﻟﻴﻪ ﺗﺨﻤﺪان اﺳـﺖ.
ﻣﻲﺷﺪ .ﺳﻨﺪرم ﻟﻴﻨﭻ ﻳﻚ اﺧﺘﻼل اﺗﻮزوﻣﺎل ﻏﺎﻟﺐ اﺳﺖ ﻛﻪ ﺗﻈﺎﻫﺮات آن
آدﻧﻮﻛﺎرﺳﻴﻨﻮﻣﺎي ﻛﻮﻟﻮن ﺑﻪ وﻳـﮋه اﻧـﻮاﻋﻲ ﻛـﻪ ﺛﺎﻧﻮﻳـﻪ ﺑـﻪ ﺳـﺮﻃﺎنﻫـﺎي
ﺑﻪ ﺻﻮرت ﺳﺮﻃﺎن اوﻟﻴﻪ ﻛﻮﻟﻮرﻛﺘﺎل و اﻧﺪوﻣﺘﺮ ﻣﻲﺑﺎﺷﺪ .اﻳﻦ اﺧـﺘﻼل ﺑـﺎ
ﺗﺨﻤﺪان ﺑﺎﺷﻨﺪ اﻏﻠﺐ در ﺗﺸﺨﻴﺺﻫﺎ ﻧﺎدﻳﺪه ﮔﺮﻓﺘﻪ ﻣﻲﺷﻮﻧﺪ .ﺗـﺸﺨﻴﺺ
اﻓﺰاﻳﺶ ﺧﻄﺮ ﺳﺮﻃﺎن در دﺳﺘﮕﺎه ﮔـﻮارش ،دﺳـﺘﮕﺎه ادراري و دﺳـﺘﮕﺎه
اﻳﻦ دو ﻋﺎرﺿﻪ از ﻫﻢ ﺑﺴﻴﺎر اﻫﻤﻴﺖ دارد ﭼﺮا ﻛﻪ درﻣـﺎنﻫـﺎي ﻣﺘﻔـﺎوﺗﻲ
ﺗﻮﻟﻴﺪ ﻣﺜﻞ زﻧﺎن ﻫﻤﺮاه اﺳﺖ .دوﻣﻴﻦ ﺳﺮﻃﺎن ﺷﺎﻳﻊ در ﻣﺒﺘﻼﻳﺎن ﺑﻪ ﺳﻨﺪرم
ﺑﺮاي آنﻫﺎ ﭘﻴﺸﻨﻬﺎد ﺷﺪه اﺳﺖ .در ﺑﺮﺧﻲ ﺳﻨﺪرمﻫﺎ ﻧﻈﻴﺮ آنﭼﻪ در ﻟﻴـﻨﭻ
ﻟﻴﻨﭻ ،ﺳﺮﻃﺎن اﻧـﺪوﻣﺘﺮﻳﺎل اﺳـﺖ .ﻣﻴـﺰان ﺧﻄـﺮ اﺑـﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎنﻫـﺎي
ﻣﻲﺑﻴﻨﻴﻢ اﻳﻦ ﻫﻢزﻣﺎﻧﻲ ﺑﻪ اﺛﺒﺎت رﺳﻴﺪه اﺳﺖ .در اﻳﻦ ﺳﻨﺪرمﻫﺎ ﻫﻢزﻣﺎﻧﻲ 12-14
ﺗـﺎﻛﻨﻮن
اﻧﺪوﻣﺘﺮﻳﺎل و ﺗﺨﻤﺪان در زﻧﺎن ﻣﺒﺘﻼ ﺑـﻪ ﺳـﻨﺪرم ﻟﻴـﻨﭻ 15-70درﺻـﺪ
ﻋﻮارض ﺗﺨﻤﺪاﻧﻲ ﺑﺎ ﭘﻮﻟﻴـﭗﻫـﺎي ﻛﻮﻟـﻮن ﻣﻄـﺮح اﺳـﺖ.
اﺳﺖ 4-6.ﺑﺮرﺳﻲ ﺳﺎﺑﻘﻪ ﻓﺎﻣﻴﻠﻲ اﻓﺮاد ﻣﺒﺘﻼ از ﻧﻈﺮ اﺑﺘﻼ ﺑﻪ ﺳﺮﻃـﺎن ﻳﻜـﻲ
ﺑﺮرﺳﻲ ﺟﺎﻣﻌﻲ ﻛﻪ ﺑﺘﻮاﻧﺪ ﻋﻜﺲ اﻳﻦ ﻗﻀﻴﻪ ﻳﻌﻨﻲ ﻫﻤﺮاﻫﻲ ﭘﻮﻟﻴـﭗﻫـﺎي
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺳﻴﻤﺎ ﺟﻌﻔﺮي و ﻫﻤﻜﺎران
127
ﻛﻮﻟﻮن ﺑﺎ ﺳﺮﻃﺎنﻫـﺎي ﺗﺨﻤـﺪاﻧﻲ را ﻧـﺸﺎن دﻫـﺪ اﻧﺠـﺎم ﻧـﺸﺪه اﺳـﺖ.
SPSSوﻳﺮاﺳﺖ 17ﺷﺪه و ﺑﺮاي ﻣﺤﺎﺳﺒﻪ ﻣﻴـﺎﻧﮕﻴﻦﻫـﺎ و ﻓﺮاواﻧـﻲﻫـﺎ از
ﺗﻔﺎوتﻫﺎي ﻧـﮋادي و ﭘـﺮاﻛﻨﺶ ﺟﻐﺮاﻓﻴـﺎﻳﻲ در ﺷـﻴﻮع و ﺑـﺮوز ﻫـﺮ دو
آﻧﺎﻟﻴﺰ ﺗﻮﺻﻴﻔﻲ اﺳﺘﻔﺎده ﮔﺮدﻳﺪ .در ﺻﻮرت ﻧﻴﺎز ﺑـﻪ ﻣﻘﺎﻳـﺴﻪ ﮔـﺮوهﻫـﺎي
ﺑﻴﻤﺎري ﺗﺎﺛﻴﺮ دارﻧﺪ ﻟﺬا اﻧﺠـﺎم ﻣﻄﺎﻟﻌـﻪاي ﺟـﺎﻣﻊ ﻛـﻪ ﺑﺘﻮاﻧـﺪ ﻫـﻢزﻣـﺎﻧﻲ
2
ﻛﻴﻔﻲ ،از ﺗﺴﺖ اﺳﺘﻔﺎده ﺷﺪ.
ﭘﻮﻟﻴﭗﻫﺎي ﻛﻮﻟﻮن را در ﺳﺮﻃﺎنﻫﺎي ﺗﺨﻤﺪاﻧﻲ ﻧـﺸﺎن دﻫـﺪ ﻋـﻼوه ﺑـﺮ اﻳﻦﻛﻪ ﺑﺮاي ﻧﺨﺴﺘﻴﻦ ﺑﺎر ﻧﺴﺒﺘﻲ واﻗﻌـﻲ از رﺧـﺪاد اﻳـﻦ دو ﺑﻴﻤـﺎري را ﻧﺸﺎن ﻣﻲدﻫﺪ ﻣﻲﺗﻮاﻧﺪ اﻫﻤﻴﺖ اﻧﺠﺎم ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ ﭘﻲﮔﻴـﺮي و ﻣﻴـﺰان وﻗﻮع ﭘﻮﻟﻴﭗﻫﺎ را ﭘﺲ از اﺑﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان ﻧﺸﺎن دﻫﺪ .ﺑـﺎ ﺗﻮﺟـﻪ
ﻳﺎﻓﺘﻪﻫﺎ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ 100ﻧﻔـﺮ ﺑـﺮ اﺳـﺎس ﻣﻌﻴﺎرﻫـﺎي ورود ﺑـﻪ ﻣﻄﺎﻟﻌـﻪ
ﺑﻪ ﺷﻴﻮع ﺑﺎﻻي ﻫﻤﺮاﻫﻲ ﺳﺮﻃﺎنﻫﺎي ﺗﺨﻤﺪان و اﻧﺪوﻣﺘﺮ ﺑﺎ ﺳﺮﻃﺎنﻫـﺎي
اﻧﺘﺨﺎب ﺷﺪﻧﺪ .ﻣﻴﺎﻧﮕﻴﻦ ﺳﻦ اﻓﺮاد 50/219/582ﺳﺎل و ﻣﻴـﺎﻧﮕﻴﻦ
ﻛﻮﻟﻮن ﻛﻪ در ﺳﻨﺪرم ﻟﻴﻨﭻ دﻳﺪه ﻣﻲﺷﻮد در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻫﺪف اﻳﻦ اﺳﺖ
در آنﻫﺎ 26/072/84kg/m2ﺑﻮد .ﺑﻴﻤﺎري اوﻟﻴﻪ در %80ﻣﻮارد ﺳـﺮﻃﺎن
ﻛﻪ ﻣﺸﺨﺺ ﻛﻨﻴﻢ آﻳﺎ در اﻓﺮادي ﻛﻪ ﺳﺮﻃﺎنﻫﺎي ﺗﺨﻤﺪان و اﻧـﺪوﻣﺘﺮﻳﺎل
ﺗﺨﻤﺪان و در %20ﻣﻮارد ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ ﺑـﻮد .ﻣﻴـﺎﻧﮕﻴﻦ زﻣـﺎن ﺳـﭙﺮي
دارﻧﺪ ﻫﻤﺮاﻫﻲ ﺑﺎ ﺳﺮﻃﺎنﻫﺎ و ﭘﻮﻟﻴﭗﻫﺎي ﻛﻮﻟﻮن ﻧﻴﺰ دﻳﺪه ﻣـﻲﺷـﻮد ﻳـﺎ
ﺷﺪه از ﺗﺸﺨﻴﺺ ﺑﻴﻤﺎري 11/125/426ﻣﺎه ﺑﻮد .ﺑﻴﺶﺗﺮﻳﻦ ﻧﻮع درﻣﺎن
ﺧﻴﺮ .ﺷﻨﺎﺧﺖ زودرس ﺳﺮﻃﺎنﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل در ﻣﺮاﺣـﻞ اوﻟﻴـﻪ ﻗﺎﺑـﻞ
اﻧﺠﺎم ﺷﺪه ﻣﺮﺑﻮط ﺑﻪ ﮔﺮوه درﻣﺎﻧﻲ ﺟﺮاﺣﻲ و ﺷﻴﻤﻲ درﻣﺎﻧﻲ ﺗﻮام ﺑﺎ 65
درﻣﺎن ﺑﻮده وﻟﻲ ﺑـﺎ ﭘﻴـﺸﺮﻓﺖ ﺑﻴﻤـﺎري ،ﭘـﻴﺶآﮔﻬـﻲ ﺑﻴﻤـﺎران ﺿـﻌﻴﻒ
درﺻﺪ ﺑﻮد %36 .اﻓﺮاد ﺳﺎﺑﻘﻪ ﻓﺎﻣﻴﻠﻲ اﺑﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎنﻫـﺎي ﺗﺨﻤـﺪان و
ﻣﻲﺷﻮد .ﺑﻨﺎﺑﺮاﻳﻦ در ﺻﻮرﺗﻲﻛﻪ اﻳـﻦ ﺳـﺮﻃﺎنﻫـﺎ در ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ ﺑـﻪ
اﻧــﺪوﻣﺘﺮ داﺷــﺘﻪ و ﺗﻨﻬــﺎ %12از اﻓــﺮاد داراي ﺳــﺎﺑﻘﻪ ﻓــﺎﻣﻴﻠﻲ اﺑــﺘﻼ ﺑــﻪ
ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ و ﺗﺨﻤﺪان ﺑﻪ ﺻﻮرت ﻫـﻢزﻣـﺎن وﺟـﻮد داﺷـﺘﻪ ﺑﺎﺷـﻨﺪ
ﺳﺮﻃﺎنﻫﺎي ﻛﻮﻟﻮرﻛﺘﺎل ﺑﻮدﻧﺪ .از ﻣﺠﻤـﻮع ﻧﻤﻮﻧـﻪﻫـﺎي ﭘـﺎﺗﻮﻟﻮژي 100
ﺷﻨﺎﺳﺎﻳﻲ زودرس آنﻫﺎ در درﻣﺎن و ﭘﻴﺶآﮔﻬﻲ ﺑﻴﻤﺎري ﻣﻮﺛﺮ ﻣﻲﺑﺎﺷﺪ.
ﺑﻴﻤﺎر ﺗﻨﻬﺎ در ﭘﻨﺞ ﻣﻮرد ﭘﻮﻟﻴﭗ ﻳﺎﻓﺖ ﮔﺮدﻳﺪ ) %60ﻣﻮارد ﺗﻮﺑـﻮﻻر و در
BMI
%40ﻣﻮارد آدﻧﻮﻣﺎﺗﻮز( .ﺳﺎﻳﺰ ﭘﻮﻟﻴﭗ در %35ﻣﻮارد زﻳﺮ ﻳﻚ ﺳـﺎﻧﺘﻲﻣﺘـﺮ
روش ﺑﺮرﺳﻲ
و در %65ﻣﻮارد زﻳﺮ 3cmﺑﻮد .ﻣﺤﻞ ﺗﻮﻣﻮر در اﻏﻠﺐ ﻣﻮارد ) (%65در ﻛﻮﻟﻮن ﺻﻌﻮدي ﺑﻮد .ﻫﺮ ﭘﻨﺞ ﺑﻴﻤﺎر ﻣﺒﺘﻼ ﺑﻪ ﭘﻮﻟﻴﭗ ،ﺳﺎﺑﻘﻪ ﻓﺎﻣﻴﻠﻲ اﺑﺘﻼ ﺑﻪ
اﻳﻦ ﻣﻄﺎﻟﻌﻪ ،ﻳﻚ ﭘﮋوﻫﺶ ﺗﻮﺻﻴﻔﻲ و ﻣﻘﻄﻌﻲ ﻣﻲﺑﺎﺷﺪ ﻛـﻪ در ﺳـﺎل
ﺳﺮﻃﺎن ﺗﺨﻤﺪان داﺷﺘﻪ و ﺳﺎﺑﻘﻪ ﻓﺎﻣﻴﻠﻲ ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل ﻧﺪاﺷﺘﻨﺪ.
1389-90اﻧﺠﺎم ﮔﺮدﻳﺪ .ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان و اﻧﺪوﻣﺘﺮ ﻛﻪ در ﺑﻴﻤﺎرﺳﺘﺎنﻫﺎي ﻓﻴﺮوزﮔﺮ ،اﻛﺒﺮ آﺑﺎدي و رﺳـﻮل اﻛـﺮم ﺗﻬـﺮان ﭘﺮوﻧـﺪه
ﺑﺤﺚ
ﺑﺴﺘﺮي داﺷﺘﻨﺪ ،اﻧﺘﺨﺎب ﺷﺪﻧﺪ .ﺑﺎ ﺑﻴﻤﺎران ﺗﻤﺎس ﺗﻠﻔﻨﻲ ﺑﺮﻗﺮار ﮔﺮدﻳﺪه و ﺗﻮﺿﻴﺢ ﻛﺎﻣﻞ در ﻣﻮرد ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ و آﻣﺎدﮔﻲﻫﺎي ﻣﺮﺑﻮط ﺑﻪ آن داده
اﺑﺘﻼي ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ اﻧﻮاع ﺳﺮﻃﺎنﻫـﺎي ﺗﺨﻤـﺪان ﺑـﻪ اﺧـﺘﻼﻻت
ﺷﺪ .ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺳـﺮﻃﺎن ﺗﺨﻤـﺪان و اﻧـﺪوﻣﺘﺮ ﻛـﻪ ﺳـﻨﺪرم FAPو
دﺳﺘﮕﺎه ﮔﻮارش و از ﺟﻤﻠﻪ اﻧﻮاع ﺣﺎﻻت ﺳﺮﻃﺎﻧﻲ و ﻳﺎ ﭘـﻴﺶ ﺳـﺮﻃﺎﻧﻲ
ﺳﻨﺪرم ﻟﻴﻨﭻ ) (HNPCCدر آنﻫﺎ ﻣﺜﺒﺖ ﺑﻮد از ﻣﻄﺎﻟﻌﻪ ﺧﺎرج ﺷﺪﻧﺪ .ﭼﻚ
ﻣﺮﺑﻮط ﺑﻪ ﻛﻮﻟﻮن از ﻣﻮاردي اﺳﺖ ﻛﻪ ﺗﺎﻛﻨﻮن ﻛﻢﺗـﺮ ﻣـﻮرد ﺗﻮﺟـﻪ ﻗـﺮار
ﻟﻴﺴﺖ ﺗﻬﻴﻪ ﺷﺪه ﺷﺎﻣﻞ ﺷﺶ ﺑﺨﺶ و 24ﺳﻮال ﺑـﻪ ﺗﺮﺗﻴـﺐ زﻳـﺮ ﺑـﻮد:
ﮔﺮﻓﺘﻪ اﺳﺖ اﻣﺎ در ﺑﺮﺧﻲ از ﺟﺪﻳﺪﺗﺮﻳﻦ ﭘـﮋوﻫﺶﻫـﺎ ﺑـﻪ ﻣﺤـﻞ ﭼـﺎﻟﺶ
اﻃﻼﻋﺎت ﻓﺮدي )ﭘﻨﺞ ﺳﻮال( ،ﻣﺸﺨﺼﺎت ﺑﻴﻤﺎري )ﻫﻔﺖ ﺳﻮال( ،ﺳـﺎﺑﻘﻪ
ﺗﺒﺪﻳﻞ ﺷﺪه اﺳﺖ .در ﻣﻄﺎﻟﻌﻪاي ﻛﻪ ﺗﻮﺳﻂ Singhﺑـﺎ ﻫـﺪف ﻏﺮﺑـﺎﻟﮕﺮي
ﻓﺎﻣﻴﻠﻲ )دو ﺳﻮال( ،وﺟﻮد ﻋﻼﻳﻢ ﻫﻤﺮاه )ﭼﻬـﺎر ﺳـﻮال( ،ﺳـﺎﺑﻘﻪ اﻧﺠـﺎم
ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل در زﻧﺎن ﻣﺒﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎن اﻧـﺪوﻣﺘﺮ اﻧﺠـﺎم ﮔﺮدﻳـﺪ،
ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ ﻗﺒﻠﻲ و زﻣﺎن آن )دو ﺳﻮال( ،ﻧﺘﻴﺠﻪ اﻧﺠﺎم ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ
ﭘﺮوﻧﺪهﻫﺎي ﭘﺰﺷﻜﻲ ﺗﻤﺎم ﺑﻴﻤﺎران زن ﻛﻪ ﺑﺎ ﺗﺸﺨﻴﺺ ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ در
ﻓﻌﻠﻲ )ﻳﻚ ﺳﻮال( ،ﻧﻮع ،ﺳﺎﻳﺰ و ﻣﺤﻞ ﭘﻮﻟﻴﭗ )ﺳﻪ ﺳﻮال( .در ﺻـﻮرت
ﺳﺎلﻫﺎي 1997ﺗﺎ 2007ﺑﺴﺘﺮي ﺷﺪه ﺑﻮدﻧﺪ ،ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺖ.
ﻳﺎﻓﺖ ﺷﺪن ﺗﻮﻣﻮر ﻳﺎ ﭘﻮﻟﻴﭗ در ﻛﻮﻟﻮن ﺗﻮﺳﻂ ﻛﻮﻟﻮﻧﻮﺳﻜﻮﭘﻲ ،ﭘﻮﻟﻴﭗﻫـﺎ
ﺳﻦ زﻣﺎن ﺗﺸﺨﻴﺺ ،ﻧﻮع ﺗﻮﻣﻮر ،ﺳـﺎﺑﻘﻪ ﻓـﺎﻣﻴﻠﻲ ﺑـﺪﺧﻴﻤﻲ ،ﻏﺮﺑـﺎﻟﮕﺮي
و ﺗﻮﻣﻮرﻫﺎ ﺑﺎ روش اﻳﻤﻮﻧﻮﻫﻴﺴﺘﻮﺷﻴﻤﻲ از ﻧﻈﺮ اوﻟﻴﻪ ﻳﺎ ﻣﺘﺎﺳﺘﺎﺗﻴﻚ ﺑﻮدن
ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل و ﻳﺎﻓﺘﻪﻫﺎي اﻳﻦ ﻏﺮﺑـﺎﻟﮕﺮي ﻣـﺸﺨﺺ ﮔﺮدﻳـﺪ267 .
آنﻫﺎ ﺑﺮرﺳﻲ ﮔﺮدﻳﺪﻧﺪ .اﻃﻼﻋﺎت ﺑﻪ دﺳﺖ آﻣﺪه از ﻣﻄﺎﻟﻌﻪ وارد ﻧﺮماﻓﺰار
زن ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ ﺑﺎ ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 66ﺳـﺎل در اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﺰﻣﻦ ﻛﻠﻴﻪJafari ﻧﺎرﺳﺎﻳﻲ درal. آﻧﺘﻲﺑﺎدي اﺧﺘﺼﺎﺻﻲ ﺑﻌﺪ از ﺗﺰرﻳﻖ واﻛﺴﻦ ﭘﻠﻲﺳﺎﻛﺎرﻳﺪي S. et
128
ﺳﺎﻟﮕﻲ ﺑﺎ اﻓـﺰاﻳﺶ ﺧﻄـﺮ ﺳـﺮﻃﺎن50 ﺗﺸﺨﻴﺺ ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ ﻗﺒﻞ از
ﺳﺎل در زﻣـﺎن ﺗـﺸﺨﻴﺺ60 آنﻫﺎ ﺳﻦ ﻛﻢﺗﺮ از%39 ﺷﺮﻛﺖ ﻛﺮدﻧﺪ ﻛﻪ
ارﺗﺒـﺎط ﻣﺸﺨـﺼﻲ در اﻓـﺰاﻳﺶ ﺧﻄـﺮ اﺑـﺘﻼ ﺑـﻪ.ﻛﻮﻟﻮرﻛﺘﺎل ﻫﻤﺮاه ﺑـﻮد
ذﻛـﺮ%2/4 در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻣﻴﺰان اﺑـﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘـﺎل.داﺷﺘﻨﺪ
ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل در زﻧﺎن ﺑﺎ ﺳﺎﺑﻘﻪ اﺑﺘﻼ ﺑﻪ ﺳـﺮﻃﺎن ﺳـﺮوﻳﻜﺲ دﻳـﺪه
ﺑﻴﺶﺗﺮﻳﻦ ﻣﻴﺰان ﺧﻄﺮ در اﺑﺘﻼي،Weinberg در ﻣﻄﺎﻟﻌﻪ15.ﮔﺮدﻳﺪه اﺳﺖ
ﻳﺎﻓﺘﻪﻫﺎي ﻣﻄﺎﻟﻌﻪ16.ﻧﺸﺪ
در ﺑﺮرﺳـﻲ16. ﺳﺎل ذﻛـﺮ ﺷـﺪه اﺳـﺖ50 ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل ﺳﻨﻴﻦ زﻳﺮ
در ﻣﻌـﺮض ﺧﻄـﺮ ﺑـﺎﻻي اﺑـﺘﻼ ﺑـﻪ،اﺑﺘﻼ ﺑﻪ ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ و ﺗﺨﻤﺪان
ﺳﺎل65 ﻧﻴﺰ ﺧﻄﺮ اﺑﺘﻼ در ﺳﻨﻴﻦ ﺑﺎﻻيNewschaffer اﻧﺠﺎم ﺷﺪه ﺗﻮﺳﻂ
ﻧﻴﺰ ارﺗﺒﺎط ﻣﺸﺨـﺼﻲJung در ﻣﻄﺎﻟﻌﻪ18.ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل ﻗﺮار دارﻧﺪ
اﻳﻦ ﻣﻄﺎﻟﻌـﺎت اﻫﻤﻴـﺖ ﺳـﻦ اﻓـﺮاد17.ﻛﺎﻫﺶ ﻣﺸﺨﺼﻲ را ﻧﺸﺎن ﻣﻲداد
ﻣﻴﺎن ﺳـﺎﺑﻘﻪ ﻓـﺎﻣﻴﻠﻲ اﺑـﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎن ﭘـﺴﺘﺎن و ﺧﻄـﺮ ﺑـﺮوز ﺳـﺮﻃﺎن
در ﺑﺮرﺳﻲ اﻧﺠﺎم.ﻣﻮرد ﺑﺮرﺳﻲ را ﺟﻬﺖ اﻧﺠﺎم ﻏﺮﺑﺎﻟﮕﺮي ﻧﺸﺎن ﻣﻲدﻫﺪ
در ﺻﻮرت در ﻧﻈﺮ ﮔﺮﻓﺘﻦ ﺧﻮﻳﺸﺎوﻧﺪان درﺟﻪ.ﻛﻮﻟﻮرﻛﺘﺎل ﺑﻪدﺳﺖ آﻣﺪ
50 ، ﻫﺰار ﻣـﻮرد ﺳـﺮﻃﺎن ﺳـﺮوﻳﻜﺲ21 ﺗﻌﺪادWeinberg ﺷﺪه ﺗﻮﺳﻂ
دوم و ﺳﻮم اﻳﻦ ارﺗﺒﺎط ﺗﻘﻮﻳﺖ ﻣﻲﻳﺎﺑﺪ و ﺳﺎﺑﻘﻪ اﺑﺘﻼ ﻓﺎﻣﻴﻠﻲ ﺑﻪ ﺳـﺮﻃﺎن
ﻫﺰار ﻣـﻮرد ﺳـﺮﻃﺎن ﺗﺨﻤـﺪان ﻣـﻮرد28 ﻫﺰار ﻣﻮرد ﺳﺮﻃﺎن اﻧﺪوﻣﺘﺮ و
ﻧﺸﺎن داد ﻛـﻪ زﻧـﺎن داراي ﺳـﺎﺑﻘﻪSchoen
RE
90
ﺑـﺎ.ﺗﺨﻤﺪان ﺑﺎﻋﺚ ﻛﺎﻫﺶ ﺧﻄﺮ اﺑﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘﺎل ﻣـﻲﮔـﺮدد
ﻧﺴﺒﺖ ﺑﺮوز اﺳﺘﺎﻧﺪارد ﺷـﺪه در ﻫـﺮ زﻳـﺮ ﮔـﺮوه از.ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺖ
اﻧﺠـﺎم،در ﻧﻈﺮ ﮔﺮﻓﺘﻦ آﻣﺎر ﭘﺎﻳﻴﻦ ﻣﺒﺘﻼﻳﺎن ﺑـﻪ ﭘﻮﻟﻴـﭗﻫـﺎي ﻛﻮﻟﻮرﻛﺘـﺎل
ﻧﻈﺮ ﺧﻄﺮ ﻧـﺴﺒﻲ اﺑـﺘﻼ ﺑـﻪ ﺳـﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘـﺎل در زﻧـﺎن داراي ﺳـﺎﺑﻘﻪ
ﻏﺮﺑﺎﻟﮕﺮي ﺗﻮﺻﻴﻪ ﻧﻤﻲﺷﻮد وﻟﻲ ﻣﻲﺗﻮاﻧﺪ در ﻏﺎﻟـﺐ ﻣﻌﻴـﺎر روﺗـﻴﻦ ﻛـﻪ
ﻳﺎﻓﺘﻪﻫﺎي ﺑﻪدﺳﺖ آﻣﺪه.ﺳﺮﻃﺎن ژﻧﻴﻜﻮﻟﻮژي ﺑﺎ ﺳﺎﻳﺮ زﻧﺎن ﻣﻘﺎﻳﺴﻪ ﮔﺮدﻳﺪ
اﻳـﻦ: ﺳﭙﺎﺳﮕﺰاري. در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﻮد،ﺑﺮاي ﺳﺎﻳﺮ اﻓﺮاد اﻧﺠﺎم ﻣﻲﮔﺮدد
ﻧﺸﺎن دﻫﻨﺪه اﻓﺰاﻳﺶ ﻣﻴـﺰان ﺑـﺮوز ﺳـﺮﻃﺎن ﻛﻮﻟﻮرﻛﺘـﺎل در زﻧـﺎن داراي
1389 ﻣﻘﺎﻟﻪ ﺑﺨﺸﻲ از ﭘﺎﻳﺎنﻧﺎﻣﻪ دﻛﺘﺮاي ﺗﺨﺼﺼﻲ رﺷـﺘﻪ داﺧﻠـﻲ ﺳـﺎل
ﺳـﺎل50 ﻣﻴﺰان ﺧﻄﺮ در زﻧﺎن زﻳـﺮ.ﺳﺎﺑﻘﻪ اﺑﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﺗﺨﻤﺪان ﺑﻮد
.ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﺑﺎ ﺣﻤﺎﻳﺖ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان اﻧﺠﺎم ﺷﺪه اﺳﺖ
. ﺳـﺎل دوﺑـﺎره رو ﺑـﻪ اﻓـﺰاﻳﺶ ﺑـﻮد64 ﺗـﺎ50 ﺑﻴﺶﺗﺮ ﺑﻮد اﻣﺎ در ﺳﻨﻴﻦ
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1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
129
ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺗﺸﺨﻴﺺ ﭘﺎﻳﺶ2012: دو روش126-129 ﻛﺎراﻳﻲ Tehran University Medical Journal; Vol. 70, No.ﺑﺮاي 2, May
Prevalence of colorectal polyps among women with ovarian and endometrial cancers admitted in Firoozgar, Akbarabadi and Rasol Akram Hospitals during 2010- 2011: a brief report Abstract Sima Jafari M.D.1* Siamak Khaleghi M.D.2 Ali Basi M.D.3 Tayeb Ramim M.D.4 1- Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2- Department of Gastrointestinal Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3- Department of Hematology Oncology Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4- Researcher, Trauma & Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Received: January 09, 2012 Accepted: January 29, 2012
Background: Patients with endometrial or ovarian cancer have an increased risk for breast or colon cancer. The aim of this study was to assess the individual and agerelated characteristics of patients with a combination of these malignancies. Methods: In this retrospective descriptive study, we reviewed the medical records of 100 patients admitted for endometrial or ovarian cancer in Rasol Akram, Akbarabadi and Firozgar educational Hospitals in Tehran, Iran, during 2010- 2011. Colon polyps were evaluated by immunohistochemistry assay. Results: The mean age, weight and BMI of the patients were 50.21, 65.9 and 26.07, respectively. Among 100 cases participating in this study, five (5%) patients had colon polyps. All the five cases with colon polyp had positive familial histories of ovarian cancer. Conclusion: With considering the low prevalence of colorectal polyps among women with ovarian and endometrial cancers, patient's follow-up for screening test is not recommended Keywords: Colorectal cancer, colorectal polyps, endometrial cancer, ovarian cancer, screening.
*
Corresponding author: Tohid Sq., Satarkhan Ave., Niyayesh St., Rasool Akram Hospital, Tehran, Iran. Tel: +98- 21- 66348529 E-mail: slr_1975@yahoo.com
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
130-135 ،1391 ﻣﺒﺘﻼ،2ﻳﺎناردﻳﺒﻬﺸﺖ ﺷﻤﺎره دورهﻴ ،70 ﭘﺰﺷﻜﻲ ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ، ﺑﺮوﺳﻠﻮزﻳﺲ ﻮﻟﻮژ،ﻳﻚ ﺗﻬﺮان ،اﭘﻴﺪﻣ ﺸﮕﺎﻫﻲ و ﻋﻠﻮم آزﻣﺎﻳ داﻧﺸﮕﺎهﺑﺎﻟﻴﻨﻲ، ﺧﺼﻮﺻﻴﺎت
130
ﺧﺼﻮﺻﻴﺎت ﺑﺎﻟﻴﻨﻲ ،آزﻣﺎﻳﺸﮕﺎﻫﻲ و اﭘﻴﺪﻣﻴﻮﻟﻮژﻳﻚ ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺑﺮوﺳﻠﻮز در اﺳﺘﺎن ﻫﻤﺪان: ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﮔﺬﺷﺘﻪﻧﮕﺮ روي 230ﺑﻴﻤﺎر :ﮔﺰارش ﻛﻮﺗﺎه
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/09/30 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/03 :
ﭼﻜﻴﺪه
1
ﭘﻴﻤﺎن ﻋﻴﻨﻲ
*3
2
ﻓﺮزاﻧﻪ اﺛﻨﻲ ﻋﺸﺮي ،اﺣﻤﺪ رﺿﺎ ﻣﺒﻴﻦ
زﻣﻴﻨﻪ و ﻫﺪف :ﺑﺮوﺳﻠﻮز ﺑﻴﻤﺎري ﺷﺎﻳﻊ ﻋﻔﻮﻧﻲ در اﻳﺮان ﺑﺎ ﺗﻈﺎﻫﺮات ﺑﺎﻟﻴﻨﻲ ﻣﺘﻨﻮع اﺳﺖ ﻛﻪ در ﺗﺸﺨﻴﺺ اﻓﺘﺮاﻗﻲ ﺑـﺴﻴﺎري
4
ﻣﻬﺪي ﺣﺴﻦ زاده
-1ﮔﺮوه ﺑﻴﻤﺎريﻫﺎي ﻋﻔﻮﻧﻲ و ﮔﺮﻣﺴﻴﺮي،
از ﺑﻴﻤﺎريﻫﺎ ﻗﺮار ﻣﻲﮔﻴﺮد .روش ﺑﺮرﺳﻲ :ﻛﻠﻴﻪ ﺑﻴﻤﺎران ﺑﺴﺘﺮيِ ﻣﺒﺘﻼ ﺑﻪ ﺑﺮوﺳﻠﻮز ﻃﻲ ﺳﺎلﻫﺎي 1384-88در ﺑﻴﻤﺎرﺳﺘﺎن
داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻫﻤﺪان ،ﻫﻤﺪان ،اﻳﺮان.
ﻓﺮﺷﭽﻴﺎن ﻫﻤﺪان ﺑﺮرﺳﻲ ﺷﺪﻧﺪ .اﻃﻼﻋﺎت از ﭘﺮوﻧﺪهﻫﺎ اﺳﺘﺨﺮاج و در ﻓﺮمﻫﺎي ﺟﻤﻊآوري ﺛﺒﺖ و ﺑﺮرﺳـﻲ آﻣـﺎري ﺷـﺪ.
-2ﮔﺮوه ﭘﺰﺷﻜﻲ اﺟﺘﻤﺎﻋﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ
ﻳﺎﻓﺘﻪ ﻫﺎ :ﺗﻌﺪاد 230ﺑﻴﻤﺎر ]) 130(%56/5ﻣﺮد و ) 100(%43/5زن[ ﺑﺎ ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 40/84±29/29ﻛـﻪ اﻛﺜـﺮاً روﺳـﺘﺎﻳﻲ
ﻫﻤﺪان ،ﻫﻤﺪان ،اﻳﺮان.
]) [167(%72/6ﺑﻮدﻧﺪ وارد ﻣﻄﺎﻟﻌﻪ ﺷﺪﻧﺪ .ﺑﻴﺶﺗﺮﻳﻦ اﺑﺘﻼ در ﻓﺼﻞ ﺑﻬﺎر ﺑﻮد .ﺷﺎﻳﻊﺗﺮﻳﻦ راه اﻧﺘﻘﺎل ) (%60/3ﻣﺼﺮف ﻣﻮاد
-3ﮔﺮوه ﺑﻴﻤﺎريﻫﺎي ﻋﻔﻮﻧﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ زﻧﺠﺎن ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ زﻧﺠﺎن،
ﻟﺒﻨﻲ ﻏﻴﺮ ﭘﺎﺳﺘﻮرﻳﺰه ﺑﻮد .ﻧﺸﺎﻧﻪﻫﺎي ﺑﺎﻟﻴﻨﻲ ﺑﻪ ﺗﺮﺗﻴﺐ ﺷﺎﻣﻞ :ﺗﺐ ،درد ﻣﻔﺎﺻﻞ ،ﺗﻌﺮﻳﻖ و ﺿﻌﻒ و ﺑﻲﺣﺎﻟﻲ ﺑﻮد .آرﺗﺮﻳﺖ و
زﻧﺠﺎن ،اﻳﺮان.
اﭘﻴﺪﻳﺪﻳﻤﻮارﻛﻴﺖ ﺑﺮوﺳﻼﻳﻲ در ) 61(%26/5و ) 21(%9/1ﺑﻴﻤﺎران ﺑﻮد .اﻓـﺰاﻳﺶ ESRدر ) 137(%59/5ﺑﻴﻤـﺎر و اﻓـﺰاﻳﺶ
-4ﻣﺮﻛﺰ ﺗﻮﺳﻌﻪ ﺗﺤﻘﻴﻘﺎت ﺑﺎﻟﻴﻨﻲ ﻓﺮﺷﭽﻴﺎن،
CRPو ﻟﻜﻮﺳﻴﺘﻮز ﺑﻪ ﺗﺮﺗﻴﺐ در ) 121(%52/9و ) 48(%20/8ﺑﻴﻤﺎران وﺟﻮد داﺷﺖ .ﻧﺘﻴﺠﻪﮔﻴﺮي :ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺗﻨﻮع ﻋﻼﻳـﻢ
داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻫﻤﺪان ،ﻫﻤﺪان ،اﻳﺮان.
ﺑﺎﻟﻴﻨﻲ ﺑﺮوﺳﻠﻮز ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ در ﺑﻴﻤﺎران ﺗـﺐدار ﺑـﺎ ﺳـﻴﺮ ﻃـﻮﻻﻧﻲ ﻳـﺎ ﻫﻤـﺮاه درﮔﻴـﺮي ارﮔـﺎنﻫـﺎ ،ﺑﺮوﺳـﻠﻮزﻳﺲ در
*
ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :زﻧﺠﺎن ،ﺧﻴﺎﺑﺎن ﻓﻀﻞاﷲ ،ﺑﻴﻤﺎرﺳﺘﺎن
وﻟﻴﻌﺼﺮ ،ﮔﺮوه ﺑﻴﻤﺎريﻫﺎي ﻋﻔﻮﻧﻲ
ﺗﺸﺨﻴﺺﻫﺎي اﻓﺘﺮاﻗﻲ ﻗﺮار ﮔﻴﺮد.
ﺗﻠﻔﻦ0241-7123303 : E-mail: amobaien@yahoo.com
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :ﺑﺮوﺳﻠﻮزﻳﺲ ،ﻋﻼﻳﻢ ﺑﺎﻟﻴﻨﻲ ،ﻧﺘﺎﻳﺞ آزﻣﺎﻳﺸﮕﺎﻫﻲ ،اﭘﻴﺪﻣﻴﻮﻟﻮژي.
درﻣﺎن ﻣﻨﺎﺳﺐ و ﺳﺮﻳﻊ ﺑﻴﻤﺎر را از ﻧـﺎﺗﻮاﻧﻲ و ﻣﻌﻠﻮﻟﻴـﺖ ﺑﻌـﺪي ﻧﺠـﺎت
ﻣﻘﺪﻣﻪ
ﺧﻮاﻫﺪ داد10.و 9ﻫﻢﭼﻨﻴﻦ ﺑﺮوﺳﻠﻮز ﺑﺎ ﻋﻮارض ﻣﺘﻌﺪدي ﻣﺎﻧﻨـﺪ ﻋـﻮارض
ﺑﺮوﺳﻠﻮز ) (Brucellosisﻳﺎ ﺗﺐ ﻣﺎﻟﺖ ﻳﻚ ﺑﻴﻤﺎري ﻣﻬﻢ ﻣﺸﺘﺮك ﺑﻴﻦ
ﮔﻮارﺷﻲ ،اﺧﺘﻼل ﺳﻴﺴﺘﻢ ﻛﺒﺪي -ﺻﻔﺮاوي ،ﻋﻮارض ﻋﺼﺒﻲ ،ﻋـﻮارض
اﻧﺴﺎن و دام اﺳﺖ ﻛﻪ از ﺣﻴﻮان آﻟﻮده ﺑﻪ اﻧﺴﺎن اﻧﺘﻘﺎل ﻣـﻲﻳﺎﺑـﺪ .ﺗﻌﺮﻳـﻖ،
ﻗﻠﺒﻲ ﻋﺮوﻗـﻲ ،ﺗﻨﻔـﺴﻲ ،ادراري ﺗﻨﺎﺳـﻠﻲ ،ﺧـﻮﻧﻲ ،ﭘﻮﺳـﺘﻲ ،ﭼـﺸﻤﻲ و
ﺗﺐ و آرﺗﺮاﻟﮋي ،ﻋﻼﻳﻢ اﺻﻠﻲ آن ﻫﺴﺘﻨﺪ ،اﻳﻦ ﺑﻴﻤﺎري ﺑﻪ ﺗﺐ ﻣﻮاج ﻧﻴـﺰ
ﻋﻮارض اﺳﺘﺨﻮاﻧﻲ ﻣﻔﺼﻠﻲ ﻫﻤﺮاه اﺳـﺖ2.و 1ﺷـﻴﻮع ﺟﻬـﺎﻧﻲ ﺑﺮوﺳـﻠﻮز
ﻣﻌﺮوف اﺳﺖ 1-3.ﺑﻴﻤﺎري ﺑﺮوﺳـﻠﻮز ﻋﻠـﻲرﻏـﻢ ﻛﻨﺘـﺮل در ﺑـﺴﻴﺎري از
اﻧﺴﺎﻧﻲ ﺑﻪ ﻋﻠﺖ دﻗﻴـﻖ ﻧﺒـﻮدن روشﻫـﺎي ﺗﺸﺨﻴـﺼﻲ و ﻧﺎﻛـﺎﻓﻲ ﺑـﻮدن
ﻛﺸﻮرﻫﺎ ﻫﻢﭼﻨﺎن ﺑﻪ ﻋﻨﻮان ﻳﻚ ﻣﻌﻀﻞ در ﻣـﺴﻴﺮ ﺳـﻼﻣﺖ ﻋﻤـﻮﻣﻲ در
ﺳﻴﺴﺘﻢ ﮔﺰارشدﻫﻲ و ﭘـﻲﮔﻴـﺮي در ﺑـﺴﻴﺎري از ﻛـﺸﻮرﻫﺎ ﻧﺎﻣـﺸﺨﺺ
ﺳﺮاﺳﺮ ﺟﻬﺎن ﻣﻄﺮح ﺑﻮده و ﻳﻜﻲ از ﻣﺴﺎﻳﻞ ﻣﻬﻢ ﺑﻬﺪاﺷﺘﻲ -اﻗﺘﺼﺎدي در
اﺳﺖ .ﺳﺎﻻﻧﻪ ﺣﺪود ﻧﻴﻢ ﻣﻴﻠﻴﻮن ﻣﻮرد ﺑﺮوﺳﻠﻮز اﻧﺴﺎﻧﻲ در ﺳﻄﺢ ﺟﻬـﺎن
ﺑــﺴﻴﺎري از ﻛــﺸﻮرﻫﺎ ﻣــﻲﺑﺎﺷــﺪ5.و 4ﺑﻴﻤــﺎري ﺑﺮوﺳــﻠﻮز ﻳــﻚ ﺑﻴﻤــﺎري
ﺑﻪ WHOﮔﺰارش ﻣﻲﺷﻮد ﻛﻪ ﻗﺴﻤﺖ اﻋﻈﻢ آن ﺧﺎص ﻛﺸﻮرﻫﺎي ﺟﻬﺎن
ﺳﻴﺴﺘﻤﻴﻚ ﺑﺎ ﺗﻈﺎﻫﺮات ﮔﻮﻧﺎﮔﻮن و ازﻣﺎن ﻣﺘﻐﻴﺮ اﺳﺖ ﺑﻪﻃﻮريﻛﻪ ﻣﻤﻜﻦ
ﺳﻮم ﻣﻲﺑﺎﺷﺪ 11.ﻃﺒﻖ آﻣﺎر اﻋﻼم ﺷﺪه از ﺳﻮي وزارت ﺑﻬﺪاﺷﺖ درﻣـﺎن
اﺳﺖ ﺑﺴﻴﺎري از ارﮔﺎنﻫﺎي ﺑـﺪن را درﮔﻴـﺮ ﻛﻨـﺪ 6.ﺑـﻴﺶﺗـﺮﻳﻦ درﺻـﺪ
و آﻣﻮزش ﭘﺰﺷﻜﻲ اﻳﺮان ،ﺗﺐ ﻣﺎﻟﺖ اﻧﺴﺎﻧﻲ در ﺳـﺎل 39 ،1384ﻣـﻮرد،
8و7و1
در ﺳﺎل 34 ،1385ﻣﻮرد و در ﺳﺎل 30 ،1386ﻣﻮرد ﺑﻪ ازاي ﻫـﺮ 100
و از آنﺟﺎ ﻛﻪ اﻳﻦ ﻋﺎرﺿﻪ ﺑﺴﻴﺎر ﻣﺨـﺮب اﺳﺖ ،ﺗﺸﺨﻴـﺺ ﺑـﻪ ﻣﻮﻗـﻊ و
ﻫﺰار ﻧﻔﺮ ﺟﻤﻌﻴﺖ ﺑﻮده 12،اﻣﺎ در ﻃﻲ ﺳﺎلﻫﺎي اﺧﻴﺮ اﻓﺰاﻳﺶ ﻳﺎﻓﺘﻪ و ﺑـﻪ
درﮔﻴﺮيﻫﺎي ﻣﻮﺿﻌﻲ در ﺳﻴﺴﺘﻢ ﻋﻀﻼﻧﻲ -اﺳﻜﻠﺘﻲ دﻳﺪه ﻣﻲﺷـﻮد
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﭘﻴﻤﺎن ﻋﻴﻨﻲ و ﻫﻤﻜﺎران
131
130در ﻫﺮ 100ﻫﺰار ﻧﻔﺮ رﺳـﻴﺪه اﺳـﺖ 3.ﻳﻜـﻲ از ﻋﻠـﻞ اﺻـﻠﻲ اﻳـﻦ
1384 -88در ﺑﻴﻤﺎرﺳﺘﺎن ﻓﺮﺷﭽﻴﺎن ﻫﻤﺪان ﺑﺴﺘﺮي ﺷﺪه ﺑﻮدﻧﺪ و ﻣـﻮرد
اﻓــﺰاﻳﺶ روﻧــﺪ را ﻧــﺎﺗﻮاﻧﻲ در رﻳ ـﺸﻪ ﻛــﻦ ﻛــﺮدن ﻛﺎﻣــﻞ آن در ﻣﻴ ـﺎن
ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺘﻨﺪ .اﻃﻼﻋﺎت دﻣﻮﮔﺮاﻓﻴﻚ و ﻣﺘﻐﻴﺮﻫـﺎي ﺳـﻦ ،ﺟـﻨﺲ،
ﮔﻮﺳﻔﻨﺪان ذﻛﺮ ﻛﺮدهاﻧـﺪ 13.در ﺿـﻤﻦ ،ﻃﻴـﻒ ﮔـﺴﺘﺮده ﻋﻼﻳـﻢ ﺑـﺎﻟﻴﻨﻲ
ﻣﻴﺰان ﺗﺤﺼﻴﻼت ،ﻓﺼﻞ اﺑﺘﻼ ،راه اﻧﺘﻘـﺎل و ﻣﺤـﻞ ﺳـﻜﻮﻧﺖ ﻋـﻼوه ﺑـﺮ
ﺑﺮوﺳﻠﻮز در اﻧﺴﺎن ﺑﺎﻋﺚ ﺷﺪه ﻛﻪ ﺗﻌﺪاد ﺑﻴﻤـﺎران ﺗـﺸﺨﻴﺺ داده ﺷـﺪه،
ﻳﺎﻓﺘﻪﻫﺎي ﺑﺎﻟﻴﻨﻲ ،ﻋـﻮارض ﺑﻴﻤـﺎري و ﻧﺘـﺎﻳﺞ آزﻣﺎﻳـﺸﮕﺎﻫﻲ ﺑﻴﻤـﺎران از
ﺑﺴﻴﺎر ﻛﻢﺗﺮ از آنﭼﻪ واﻗﻌﺎً ﻣـﻲﺑﺎﺷـﻨﺪ ﺗﺨﻤـﻴﻦ زده ﺷـﻮد15.و 14در ﻫـﺮ
ﭘﺮوﻧﺪهﻫﺎ اﺳﺘﺨﺮاج و در ﭘﺮﺳﺶﻧﺎﻣﻪﻫﺎﻳﻲ ﻛﻪ ﺑﻪ ﻫﻤﻴﻦ ﻣﻨﻈـﻮر ﻃﺮاﺣـﻲ
ﺻﻮرت ،ﻫﻨﻮز اﻳﺮان در ﺷﻤﺎر ﻣﻨﺎﻃﻖ اﻧﺪﻣﻴﻚ ﺑﻪ ﺣـﺴﺎب ﻣـﻲآﻳـﺪ 12.از
ﺷﺪه ﺑﻮد ،ﺛﺒﺖ و ﻧﺘﺎﻳﺞ ﺑﻪ ﺻﻮرت آﻣﺎر ﺗﻮﺻﻴﻔﻲ اراﻳﻪ ﮔﺮدﻳﺪ و ﭘـﺲ از
ﻋﻠﻞ اﻧﺘﺸﺎر ﺗﺐ ﻣﺎﻟﺖ در اﻳﺮان زﻧﺪﮔﻲ روﺳﺘﺎﻳﻲ و ﻋـﺸﺎﻳﺮي اﺳـﺖ در
ﺟﻤﻊآوري اﻃﻼﻋﺎت ﺑﺮاي ﺗﻮﺻﻴﻒ ﻣﺘﻐﻴﺮ ﻛﻤﻲ از ﻣﻴﺎﻧﮕﻴﻦ و ﺣـﺪاﻗﻞ و
اﻳﻦ ﻣﻘﺎﻃﻊ ،ﺑﻴﻦ ﻣﺤﻞ زﻧﺪﮔﻲ ﺧﺎﻧﻮادهﻫﺎ و ﻣﺤـﻞ ﻧﮕـﻪداري ﮔﻮﺳـﻔﻨﺪان
ﺣﺪاﻛﺜﺮ و ﺑﺮاي ﻣﺘﻐﻴﺮ ﻛﻴﻔﻲ از ﻓﺮاواﻧـﻲ اﺳـﺘﻔﺎده ﺷـﺪ .ﻣﻌﻴـﺎر ورود ﺑـﻪ
ﻓﺎﺻﻠﻪ ﭼﻨﺪاﻧﻲ وﺟﻮد ﻧﺪارد و ﻧﻮازش ﻧﻮزاد ﺗﺎزه ﺑﻪ دﻧﻴﺎ آﻣﺪه دام ﺗﻮﺳﻂ
ﻣﻄﺎﻟﻌﻪ ﺗﺸﺨﻴﺺ ﻗﻄﻌﻲ ﺑﻴﻤﺎري ﺑﺎ ﺳﺮوﻟﻮژي ﻣﻨﻄﺒﻖ ﺑـﺮ ﻋﻼﻳـﻢ ﺑـﺎﻟﻴﻨﻲ
ﻛﻮدﻛﺎن و ﻣﺼﺮف ﻣﺤﺼﻮﻻت ﻟﺒﻨﻲ و ﺗﺎزه ﺗﻬﻴﻪ ﺷﺪه داﻣﻲ و ﻫـﻢﭼﻨـﻴﻦ
ﺑﻮد .در ﺻﻮرﺗﻲ ﻛﻪ ﺗﺸﺨﻴﺺ ﺑﺮ اﺳﺎس ﻇﻦ ﺑﺎﻟﻴﻨﻲ و ﭘﺎﺳـﺦ ﺑـﻪ درﻣـﺎن
ذﺑﺢ ﻏﻴﺮ اﺳﺘﺎﻧﺪارد دامﻫﺎ از اﻫﻤﻴﺖ ﺑﺎﻻﻳﻲ در ﺑﻴﻤـﺎريزاﻳـﻲ ﺑﺮﺧـﻮردار
ﺑﻮده و ﺳﺮوﻟﻮژي ﺗﺎﻳﻴﺪﻛﻨﻨﺪه ﻧﺒﻮد ،از ﻣﻄﺎﻟﻌﻪ ﺣﺬف ﻣﻲﺷﺪ.
اﺳﺖ 3.ﺗﺴﺖﻫﺎي آزﻣﺎﻳﺸﮕﺎﻫﻲ ﻣﺨﺘﻠﻔﻲ از ﺟﻤﻠﻪ آﻧﺘﻲﺑﺎدي اﺧﺘـﺼﺎﺻﻲ ﺿﺪ ﺑﺮوﺳﻼ ،روشﻫﺎي ﺗﺸﺨﻴﺼﻲ ﻣﻮﻟﻜﻮﻟﻲ ﻣﺎﻧﻨﺪ PCRو ﺟﺪاﺳﺎزي و 16
ﻳﺎﻓﺘﻪﻫﺎ
ﻛﺸﺖ ﺑﺮوﺳﻼ از ﻧﻤﻮﻧﻪ ﮔﺮﻓﺘﻪ ﺷﺪه ،ﺑـﺮاي ﺗـﺸﺨﻴﺺ وﺟـﻮد دارﻧـﺪ.
ﺑﻌﻀﻲ از اﻳﻦ آزﻣﺎﻳﺸﺎت را ﻧﻤﻲﺗﻮان ﺑﻪ ﻋﻨﻮان اﺑﺰار آزﻣﺎﻳﺸﮕﺎﻫﻲ روﺗﻴﻦ
در اﻳﻦ ﻣﻄﺎﻟﻌﻪ 230ﺑﻴﻤﺎر ]) 130(%56/5ﻣـﺮد و ) 100(%43/5زن[
ﺑﻪ وﻳﮋه در ﻛﺸﻮرﻫﺎي در ﺣﺎل ﺗﻮﺳﻌﻪ ﻛﻪ اﻧﺪﻣﻴﻚ ﺑﺮوﺳﻠﻮز ﻫـﺴﺘﻨﺪ ﺑـﻪ
ﺑﺎ ﻣﻴﺎﻧﮕﻴﻦ ﺳﻨﻲ 40/84±20/29و ﻣﺤﺪوده ﺳـﻨﻲ 9ﺗـﺎ 88ﺳـﺎل ﺳـﻦ،
ﻛﺎر ﮔﺮﻓﺖ .ﻫﺮ ﭼﻨﺪ اﺳﺘﻔﺎده از ﻛـﺸﺖ ﺧـﻮن ﻣﺮﺳـﻮم ﻛﺎﺳـﺘﺎﻧﺪا ﺑـﺮاي
وارد ﻣﻄﺎﻟﻌﻪ ﺷﺪﻧﺪ .در اﻳﻦ ﺟﻤﻌﻴﺖ 75 ،ﺑﻴﻤﺎر ) (%39/7ﺳـﺎﺑﻘﻪ ﺗﻤـﺎس
ﺑﺮوﺳﻼ ﻣﺸﻜﻼت ﻣﺘﻌﺪدي دارد ،ﺑﻪ ﻫﺮ ﺣﺎل راه ﺗﺎﻳﻴﺪ ﺗﺸﺨﻴﺺ ﻋﻔﻮﻧﺖ
ﺑﺎ دام و 114ﺑﻴﻤﺎر ) (%60/3ﺳﺎﺑﻘﻪ ﻣﺼﺮف ﻣﻮاد ﻟﺒﻨﻲ را داﺷـﺘﻨﺪ .اﻛﺜـﺮ
ﺣﺎد ﺑﺮوﺳﻠﻮز ﻛﺸﺖ ﻣﻲﺑﺎﺷﺪ 16.از آنﺟـﺎﻳﻲﻛـﻪ ﺑﻴﻤـﺎري ﺑﺮوﺳـﻠﻮز در
ﺑﻴﻤﺎران ] 166ﻧﻔﺮ ) [(%72/2ﺳﺎﻛﻦ روﺳﺘﺎ ﺑﻮدﻧﺪ .ﻓﺮاواﻧﻲ اﺑـﺘﻼ ﻓـﺼﻠﻲ
ﻛﺸﻮرﻫﺎي ﺧﺎورﻣﻴﺎﻧﻪ ،ﻣﺪﻳﺘﺮاﻧﻪ و ﺣﺎﺷﻴﻪ ﺧﻠﻴﺞ ﻓﺎرس از ﺟﻤﻠﻪ اﻳﺮان ﺑﻪ
ﺑﻪ ﺑﺮوﺳﻠﻮز در ﺑﻴﻤﺎران ﺗﺤـﺖ ﻣﻄﺎﻟﻌـﻪ ﺑـﻪ ﺗﺮﺗﻴـﺐ در ﺑﻬـﺎر )،(%33/6
وﻓﻮر ﻳﺎﻓﺖ ﻣﻲﺷﻮد 3و در ﻣﻴﺎن ﺷـﻬﺮﻫﺎي اﻳـﺮان ﻧﻴـﺰ ،اﻳـﻦ ﺑﻴﻤـﺎري در
ﺗﺎﺑﺴﺘﺎن ) ،(%29/6ﭘﺎﻳﻴﺰ ) (%18/8و زﻣﺴﺘﺎن ) (%17/9ﺑﻮد )ﺟـﺪول .(1
اﺳﺘﺎن ﻫﻤﺪان ﺷﻴﻮع ﺑﺎﻻﻳﻲ دارد و ﻋﺪم آﮔﺎﻫﻲ از وﺿـﻌﻴﺖ ﺑﻴﻤـﺎري در
ﺑﻴﺶﺗﺮﻳﻦ ﻋﻼﻣـﺖ ﺑـﺎﻟﻴﻨﻲ ﻛـﻪ در اﻳـﻦ ﺑﻴﻤـﺎران وﺟـﻮد داﺷـﺖ ،ﺗـﺐ
ﻣﻨﻄﻘﻪ و ﺑﻪ ﻣﻨﻈﻮر ﺑﻪ روز ﻛﺮدن اﻃﻼﻋﺎت و ﺗﻌﻴﻴﻦ ﻓﺮاواﻧﻲ ﻧـﺸﺎﻧﻪﻫـﺎي
) (%77/4و ﺳﭙﺲ ،درد ﻣﻔﺼﻠﻲ) (%70ﺑﻮد )ﻧﻤﻮدار 55(%24) .(1ﻧﻔﺮ از
ﺑﺎﻟﻴﻨﻲ و ﻳﺎﻓﺘﻪﻫﺎي ﺳﺮوﻟﻮژي ﻣﺮﺑﻮط ﺑﻪ اﻳﻦ ﺑﻴﻤﺎري ،ﻣﻄﺎﻟﻌـﻪاي در اﻳـﻦ
ﺑﻴﻤﺎران ،دﭼﺎر ﺑﺮوﺳﻠﻮز ﺣﺎد ﺑﻮدﻧﺪ و ﻃﻮل ﻣﺪت ﺑﻴﻤﺎرﻳـﺸﺎن ﻛـﻢﺗـﺮ از
زﻣﻴﻨﻪ ﻃﺮاﺣﻲ ﺷﺪ ﺗﺎ از ﻧﺘﺎﻳﺞ آن در ﺳﻴﺴﺘﻢ ﺑﻬﺪاﺷﺘﻲ -درﻣﺎﻧﻲ اﺳـﺘﻔﺎده
ﺳﻪ ﻣﺎه ﺑﻮد .اﻛﺜﺮ ﺑﻴﻤـﺎران ]) 163(70/8ﺑﻴﻤـﺎر[ ﺑـﻪ ﺷـﻜﻞ ﺗﺤـﺖ ﺣـﺎد
ﺷﻮد و ﻛﻤﻚ ﺑﻪ ﺗﺸﺨﻴﺺ و درﻣﺎن ﺑﻪ ﻣﻮﻗﻊ ﺑﺮاي ﺟﻠـﻮﮔﻴﺮي از ﻣـﺰﻣﻦ
ﺑﺮوﺳﻠﻮز ﻣﺒﺘﻼ ﺑﻮدﻧﺪ و ﻃﻮل ﻣﺪت ﺑﻴﻤﺎرﻳﺸﺎن ﺗﺎ ﻗﺒﻞ از ﻣﺮاﺟﻌﻪ ﺑﻴﻦ ﺳﻪ
ﺷﺪن و ﻋﻮارض ﺑﻌﺪي ﺑﻴﻤﺎري ﺑﺮوﺳﻠﻮز ﺷﻮد.
ﻣﺎه ﺗﺎ ﻳﻚﺳﺎل ﺑﻮد .ﺗﻨﻬﺎ 12ﺑﻴﻤﺎر ) (%5/2ﺳﺎﺑﻘﻪ ﺑﻴﻤـﺎري ﺑـﻴﺶ از ﻳـﻚ ﺳﺎل داﺷﺘﻨﺪ و ﺑﻪ ﻧﻮع ﻣﺰﻣﻦ ﺑﺮوﺳﻠﻮز ﻣﺒﺘﻼ ﺑﻮدﻧﺪ .از ﻧﻈـﺮ ﺗﺤـﺼﻴﻼت،
روش ﺑﺮرﺳﻲ
106ﻧﻔﺮ ) (%50/7زﻳﺮ دﻳﭙﻠﻢ ﺑﻮدﻧﺪ و ﻓﻘﻂ ﺷﺶ ﻧﻔﺮ ) (%2/9از ﺑﻴﻤﺎران ﺗﺤﺼﻴﻼت ﻓﻮق دﻳﭙﻠﻢ داﺷﺘﻨﺪ )ﺟﺪول 146 .(1ﺑﻴﻤـﺎر ) (%63/4دﭼـﺎر
ﺑﺎ ﻃﺮاﺣﻲ ﻳﻚ ﻣﻄﺎﻟﻌﻪ ﺗﻮﺻﻴﻔﻲ ﮔﺬﺷﺘﻪﻧﮕﺮ ،ﭘﺮوﻧﺪه ﻛﻠﻴﻪ ﺑﻴﻤﺎراﻧﻲﻛﻪ
ﻋﺎرﺿﻪ ﺷﺪﻧﺪ ﺑﻪ ﻃﻮريﻛﻪ اﺳﭙﻮﻧﺪﻳﻠﻴﺖ ﺑﺎ 61ﺑﻴﻤﺎر) (%26/5ﺑﻴﺶﺗـﺮﻳﻦ
ﺷﻜﺎﻳﺎت ﺑﺎﻟﻴﻨﻲ ﻣﻨﻄﺒﻖ ﺑﺎ ﺑﺮوﺳﻠﻮز ﻫﻤﺮاه ﺑﺎ آزﻣﺎﻳﺶ راﻳﺖ ﺑـﻴﺶﺗـﺮ ﻳـﺎ
و ﻣﻨﻨﮋﻳﺖ ﺑﺎ ﻫﻔﺖ ﺑﻴﻤﺎر ) (%3ﻛـﻢﺗـﺮﻳﻦ آﻣـﺎر را ﺑـﻪ ﺧـﻮد اﺧﺘـﺼﺎص
ﻣﺴﺎوي 1/80ﻳﺎ ﻛﻮﻣﺒﺲ راﻳﺖ ﺑﺎﻻي ) 1/40ﻫﻨﮕـﺎﻣﻲﻛـﻪ راﻳـﺖ ﻣﻨﻔـﻲ
ﻣﻲدادﻧﺪ )ﺟﺪول .(1از ﻧﻈـﺮ ﺑﺮرﺳـﻲ آزﻣﺎﻳـﺸﮕﺎﻫﻲ ،ﺗﻌـﺪاد ﻟﻜﻮﺳـﻴﺖ
ﺑﻮد( ﻫﻤﺮاه ﺑﺎ 2ME≥1/40داﺷﺘﻨﺪ و ﺑﺎ ﺗﺸﺨﻴﺺ ﺑﺮوﺳﻠﻮز ﻃﻲ ﺳﺎلﻫﺎي
ﺑﻴﻤﺎران در اﻛﺜﺮ ﻣﻮارد ]) 170(%76/9ﺑﻴﻤﺎر[ در ﻣﺤﺪوده ﻃﺒﻴﻌﻲ ﺑﻮد.
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﺧﺼﻮﺻﻴﺎت ﺑﺎﻟﻴﻨﻲ ،آزﻣﺎﻳﺸﮕﺎﻫﻲ و اﭘﻴﺪﻣﻴﻮﻟﻮژﻳﻚ ﻣﺒﺘﻼﻳﺎن ﺑﺮوﺳﻠﻮزﻳﺲ
132
ﻧﻤﻮدار :1 -درﺻﺪ ﻓﺮاواﻧﻲ ﻋﻼﻳﻢ ﺑﺎﻟﻴﻨﻲ در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺗﺐ ﻣﺎﻟﺖ ﺑﺴﺘﺮي
ﻧﻤﻮدار :2 -درﺻﺪ ﻓﺮاواﻧﻲ ﻳﺎﻓﺘﻪﻫﺎي آزﻣﺎﻳﺸﮕﺎﻫﻲ در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺗﺐ ﻣﺎﻟﺖ
ﺟﺪول :1 -ﻓﺮاواﻧﻲ ﻣﺒﺘﻼﻳﺎن ﺗﺐﻣﺎﻟﺖ ﺑﺮ ﺣـﺴﺐ ﻣﺘﻐﻴﺮﻫـﺎي ﺟـﻨﺲ ،ﺳـﻦ ،ﻣﺤـﻞ
46ﻧﻔﺮ ) (%20/8ﻟﻜﻮﺳﻴﺘﻮز داﺷﺘﻨﺪ و ﺗﻨﻬﺎ ﭘـﻨﺞ ﻧﻔـﺮ ) (%2/3ﻟﻜﻮﭘﻨﻴـﻚ
زﻧﺪﮔﻲ ،ﺗﻤﺎس ﺑﺎ دام ،ﻣﺼﺮف ﻟﺒﻨﻴﺎت )ﻏﻴﺮﭘﺎﺳﺘﻮرﻳﺰه( ،ﺗﺤﺼﻴﻼت و ﻋﺎرﺿﻪ ﺑﻴﻤﺎري ﺗﻌﺪاد )درﺻﺪ(
ﻣﺘﻐﻴﺮ
ﺷﺪه ﺑﻮدﻧﺪ .ﺷﺎﻳﻊﺗﺮﻳﻦ ﻳﺎﻓﺘﻪ آزﻣﺎﻳﺸﮕﺎﻫﻲ ﺑﻪدﺳـﺖ آﻣـﺪه اﻓـﺰاﻳﺶ
ESR
در %59/5ﺑﻴﻤﺎران و ﺳـﭙﺲ اﻓـﺰاﻳﺶ CRPدر %52/9از ﺑﻴﻤـﺎران ﺑـﻮد.
ﻣﺮد
)130(56/5
زن
)100(43/5
0-20
)50(21/7
21-40
)69(30
41-60
)62(27
61-80
)45(19/6
<80
)4(1/7
ﺷﻬﺮ
)64(23/8
ﺑﺮﺧﻼف ﻣﻄﺎﻟﻌﻪﻫﺎﻳﻲ ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﻗﺒﻼ در ﻋﺮﺑﺴﺘﺎن و ﻫﻢﭼﻨﻴﻦ در اﻳﺮان
روﺳﺘﺎ
)166(72/2
اﻧﺠﺎم ﺷﺪه ﺑﻮد
19
دارد
)75(39/7
ﻟﻴﺒﻲ 20و اﺧﻴﺮاً در اﻳـﺮان ﻛـﻪ ﺗﻮﺳـﻂ 21Haj Abdolbaghiاﻧﺠـﺎم ﺷـﺪه،
ﻧﺪارد
)155(60/3
ﺳﺎﺑﻘﻪ ﻣﺼﺮف ﻣﻮاد ﻟﺒﻨﻲ
دارد
)114(60/3
ﻏﻴﺮ ﭘﺎﺳﺘﻮرﻳﺰه
ﻧﺪارد
)116(39/7
ﺑﻲﺳﻮاد
)82(35/9
ﺟﻨﺲ
ﺳﻦ
ﻣﺤﻞ زﻧﺪﮔﻲ
ﺳﺎﺑﻘﻪ ﺗﻤﺎس ﺑﺎ دام
ﻣﻴﺰان ﺗﺤﺼﻴﻼت
ﻋﺎرﺿﻪ
ﻟﻜﻮﺳـــﻴﺘﻮز در %20/8و آﻧﻤـــﻲ در %14/7و ﻟﻨﻔﻮﺳـــﻴﺘﻮز در %13/6 ﺑﻴﻤﺎران وﺟﻮد داﺷﺖ )ﻧﻤﻮدار .(2
ﺑﺤﺚ در اﻳﻦ ﺗﺤﻘﻴﻖ اﻛﺜﺮ ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺑﺮوﺳـﻠﻮز ﻣـﺮد ﺑﻮدﻧـﺪ و اﻳـﻦ 18و17
اﻣﺎ در اﻏﻠﺐ ﻣﻄﺎﻟﻌﺎت دﻳﮕـﺮ از ﺟﻤﻠـﻪ در ﻟﺒﻨـﺎن،
ﺑﻴﻤﺎري ﺑﺮوﺳﻠﻮز در ﻣﺮدان ﺑﻴﺶﺗﺮ از زﻧﺎن ﮔﺰارش ﺷﺪه .ﻣﻤﻜـﻦ اﺳـﺖ ﻳﻜﻲ از دﻻﻳﻞ ﺑﻪ دﺳﺖ آﻣﺪن اﻳﻦ ارﺟﺤﻴﺖ ،اﻧﺘﻘﺎل ﺷﻐﻠﻲ اﻳـﻦ ﺑﻴﻤـﺎري ﺑﺎﺷﺪ ،ﮔﺮﭼﻪ در ﻣﻨﺎﻃﻖ اﻧﺪﻣﻴﻚ اﻳﻦ ﺑﻴﻤﺎري اﻏﻠﺐ زﻧﺎن ﻧﻴﺰ ﻣﺎﻧﻨﺪ ﻣﺮدان ﺑﻪ ﻛﺸﺎورزي و دام داري ﻣﺸﻐﻮﻟﻨﺪ اﻣﺎ ﻣﺸﺎرﻛﺖ آنﻫﺎ در اﻳﻦ ﻣﺸﺎﻏﻞ و
زﻳﺮ دﻳﭙﻠﻢ
)117(50/7
دﻳﭙﻠﻢ
)24(10/5
ﻣﺘﻌﺎﻗﺒﺎً ﺗﻤﺎس آنﻫﺎ ﻧﻴﺰ ﻛﻢﺗﺮ از ﻣﺮدان ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ .از ﻧﻈﺮ ﻣﺤـﺪوده
داﻧﺸﮕﺎﻫﻲ
)7(2/9
ﺳﻨﻲ ،ﺑﻴﺸﺘﺮ ﻣﺒﺘﻼﻳﺎن در دﻫﻪ ﺳﻮم و ﭼﻬﺎرم زﻧﺪﮔﻲ ﺑﻮدﻧﺪ ،ﻛﻪ ﺑـﺎ ﺳـﺎﻳﺮ
آرﺗﺮﻳﺖ
)57(24/8
ﻣﻄﺎﻟﻌﺎت اﻧﺠﺎم ﺷﺪه در ﻛـﺸﻮرﻫﺎي ﻣﺠـﺎور ﻣﺎﻧﻨـﺪ ﺗﺮﻛﻴـﻪ و ﻋﺮﺑـﺴﺘﺎن
اﺳﭙﻮﻧﺪﻳﻠﻴﺖ
)61(26/5
ﻣﻄﺎﺑﻘﺖ دارد.
اﭘﻴﺪﻳﺪﻳﻤﻴﻮارﻛﻴﺖ
)21(9/2
ﻣﻮاد ﻟﺒﻨﻲ ﻏﻴﺮﭘﺎﺳﺘﻮرﻳﺰه ﺑﻮد ﻛﻪ اﮔﺮﭼﻪ ﺑﻪ ﺑﻌـﻀﻲ ﻣﻄﺎﻟﻌـﺎت ﺑـﺎ 67/9و
ﻣﻨﻨﮋﻳﺖ
)7(3
66/7درﺻﺪ ،ﻧﺰدﻳﻚ ﺑﻮد22.و 21اﻣﺎ در ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﺑﻌﻀﻲ ﻣﻄﺎﻟﻌﺎت ﻗﺒﻠﻲ ﺑﺎ
ﻧﺪارد
)84(36/5
76/4و 88/3درﺻﺪ ،ﻛﻢﺗﺮ ﺑﻮد23.و 20درﺻـﺪي از اﻳـﻦ ﻛـﺎﻫﺶ ﻣﻴـﺰان
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
22و20و17
در اﻳﻦ ﻣﻄﺎﻟﻌﻪ %60/3ﻣﻮارد ﻋﻠﺖ اﺑﺘﻼ ،ﻣـﺼﺮف
ﻫﻤﻜﺎران ﻋﻴﻨﻲ و Eini P. ﭘﻴﻤﺎنet al.
اﺑﺘﻼ از اﻳﻦ راه ،ﻣﻲﺗﻮاﻧﺪ ﻧﺎﺷﻲ از آﮔﺎﻫﻲ ﻣﺮدم در راﺑﻄﻪ ﺑـﺎ ﺟﻮﺷـﺎﻧﺪن
133
ﻣﺨﺘﺼﺮ ﻳﺎ ﺑﺪون دﻳﺰاوري ﻣﻲﮔﺮدد .ﺑﺮرﺳﻲ ادرار اﻳﻦ ﺑﻴﻤـﺎران ﻣﻌﻤـﻮﻻ 1
ﺷﻴﺮ ﺑﺎﺷﺪ و ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ ﻛﻪ ﺑﺎ ﮔﺬر زﻣﺎن از درﺻﺪ ﻓﺮاواﻧﻲ اﻳـﻦ راه
ﻃﺒﻴﻌــﻲ اﺳــﺖ و ﻛــﺸﺖ ﻣﻌﻤــﻮل ادرار ،ﻣﻨﻔــﻲ ﻣــﻲﺑﺎﺷــﺪ .ﻓﺮاواﻧــﻲ
اﻧﺘﻘﺎل ﻛﺎﺳﺘﻪ ﺷﻮد .در ﺗﺤﻘﻴﻖ ﺣﺎﺿﺮ ،ﻣﻴﺰان ﺗﻤﺎس ﺑﺎ دام ﺣﺪود %39/7
اﭘﻴﺪﻳﺪﻳﻤﻮاورﻛﻴﺖ در اﻳﻦ ﺑﺮرﺳﻲ %9/2ﺑﻮد .در دﻳﮕﺮ ﻣﻄﺎﻟﻌـﺎت اﻧﺠـﺎم
ﺑﺮآورد ﺷﺪ .در ﺳﻪ ﻣﻄﺎﻟﻌﻪ دﻳﮕﺮ ﻛﻪ در اﻳﺮان اﻧﺠﺎم ﺷﺪه ﺑـﻮد 27 ،17/1
ﺷﺪه در اﻳﺮان 10/9و 7/4درﺻﺪ ﮔﺰارش ﺷﺪه اﺳـﺖ23.و 22در ﻣﻄﺎﻟﻌـﻪ
و 34/25درﺻﺪ را ﺑﻪدﺳﺖ آورده ﺑﻮدﻧﺪ23و 21و در ﺳـﺎﻳﺮ ﻣﻄﺎﻟﻌـﺎت در
ﺣﺎﺿﺮ ،ﺗﻐﻴﻴﺮات ﻫﻤﺎﺗﻮﻟﻮژﻳﻚ ﺑـﻪ ﺻـﻮرت %20/8ﻟﻜﻮﺳـﻴﺘﻮز%13/6 ،
ﻛــﺸﻮرﻫﺎي ﻣﺠــﺎور آﻣــﺎري ﺑــﻴﻦ 32ﺗــﺎ 71درﺻــﺪ ﮔــﺰارش ﺷــﺪه
ﻟﻨﻔﻮﺳﻴﺘﻮز و %14/7آﻧﻤﻲ ﺑـﻮد و اﻓـﺰاﻳﺶ ESRو CRPﺑـﻪ ﺗﺮﺗﻴـﺐ در
اﺳﺖ22.و20و 19ﺑﻨﺎﺑﺮاﻳﻦ ﮔﺮﭼﻪ ﺷﻐﻞ ﻳﻚ ﻋﺎﻣﻞ ﺧﻄﺮ ﻣﺤﺴﻮب ﻣـﻲﺷـﻮد،
%59/5و %52/9از ﺑﻴﻤﺎران وﺟﻮد داﺷﺖ .اﻳﻦ در ﺣـﺎﻟﻲ اﺳـﺖ ﻛـﻪ در
اﻣﺎ ﺑﻪ ﻧﻈﺮ ﻧﻤﻲرﺳﺪ ﻛﻪ در ﻛﺸﻮرﻫﺎي ﺟﻬﺎن ﺳﻮم ﺑﻴﻤﺎري اﻟﺰاﻣـﺎً ﺷـﻐﻠﻲ
ﻣﻄﺎﻟﻌﻪ Haddadiدر ﺗﻬﺮان ،اﻛﺜﺮ ﺑﻴﻤﺎران ﺗﻐﻴﻴـﺮات ﻫﻤﺎﺗﻮﻟﻮژﻳـﻚ ﺑـﺎرز
ﺑﺎﺷﺪ و ﻋﻮاﻣﻞ دﺧﻴﻞ دﻳﮕﺮي ﻧﻴﺰ وﺟﻮد دارد .ﻓﺼﻞ ﺑﻬﺎر و ﺗﺎﺑﺴﺘﺎن ﻛـﻪ
ﻧﺪاﺷــﺘﻨﺪ و در اﻛﺜــﺮ ﻣــﻮارد CBCﺑﻴﻤــﺎران ﻧﺮﻣــﺎل ﺑــﻮد 22.از ﻧﻈــﺮ
ﻓﺼﻞ زاﻳﺶ دامﻫﺎﺳﺖ ،ﺷﺎﻳﻊﺗـﺮﻳﻦ ﻓـﺼﻮل اﺑـﺘﻼ ﺑﻮدﻧـﺪ ﻛـﻪ ﺑـﺎ ﺳـﺎﻳﺮ
آزﻣﺎﻳﺸﮕﺎﻫﻲ Namiduru ،در ﺗﺮﻛﻴﻪ ﺷﺎﻳﻊﺗـﺮﻳﻦ ﺗﻐﻴﻴـﺮ ﻫﻤﺎﺗﻮﻟﻮژﻳـﻚ را
ﻣﻄﺎﻟﻌﺎت ﻣﻄﺎﺑﻘﺖ داﺷﺖ 23-25.ﺳﻜﻮﻧﺖ در روﺳﺘﺎ ﺑﺎ ﻓﺮاواﻧﻲ %72/2در
ﻟﻨﻔﻮﻣﻮﻧﻮﺳﻴﺘﻮز و ﺳﭙﺲ آﻧﻤﻲ ﮔـﺰارش ﻛـﺮد .در ﻣﻄﺎﻟﻌـﻪ
18
ﻣﺒﺘﻼﻳﺎن ﺑﺎ ﻣﻄﺎﻟﻌﻪ 23Haddadi 21،Haj Abdolbaghiﻛﻪ ﻗﺒﻼً اﻧﺠﺎم ﺷـﺪه
%84/5ﺑﻴﻤﺎران ﺗﻌﺪاد ﮔﻠﺒﻮل ﺳﻔﻴﺪ ﻧﺮﻣﺎل داﺷـﺘﻨﺪ و CRP %60/4ﻣﺜﺒـﺖ
ﺑﻮد ﻣﻄﺎﺑﻘﺖ ﻧﺪاﺷﺖ و ﺧﻴﻠﻲ ﺑﻴﺶﺗﺮ از آنﻫـﺎ ﺑـﻮد ) %15/67و %40/5
ﺑﻮدﻧﺪ ﻛﻪ ﺗﻘﺮﻳﺒﺎً ﺑﺎ ﻣﻄﺎﻟﻌـﻪ ﺣﺎﺿـﺮ ﻫـﻢﺧـﻮاﻧﻲ داﺷـﺖ اﻣـﺎ ESRرا در
در ﺟﻤﻌﻴﺖ روﺳﺘﺎﻳﻲ( .اﻳﻦ ﺗﻔـﺎوت ﺷـﺎﻳﺪ ﻧﺎﺷـﻲ از اﻳـﻦ ﺑـﻮد ﻛـﻪ دو
%80/7ﻣﻮارد ﻧﺮﻣﺎل ﮔﺰارش ﻛﺮده ﺑـﻮد ﻛـﻪ ﺑـﺎ ﻣﻄﺎﻟﻌـﻪ ﻣـﺎ ﺗﻘﺮﻳﺒـﺎً %19
ﻣﻄﺎﻟﻌﻪ ذﻛﺮ ﺷﺪه در ﻣﺮاﻛـﺰ درﻣـﺎﻧﻲ ﺗﻬـﺮان اﻧﺠـﺎم ﺷـﺪه ﺑـﻮد .در اﻳـﻦ
ﺗﻔﺎوت داﺷﺖ.
26
Roushan
ﻣﻄﺎﻟﻌﻪ ،ﻣﻴﺰان ﺗﺤﺼﻴﻼت ﻓـﺎﻛﺘﻮر ﻣﻔﻴـﺪي در ﺟﻠـﻮﮔﻴﺮي از اﺑـﺘﻼ ﺑـﻮد
ﺑﺮوﺳﻼ از ﺟﻤﻠﻪ ارﮔﺎﻧﻴﺴﻢﻫﺎي درون ﺳﻠﻮﻟﻲ اﺳـﺖ ﻛـﻪ ﻣـﻲﺗﻮاﻧـﺪ
ﺑﻪﻃﻮريﻛﻪ داﺷﺘﻦ ﻣﺪرك دﻳﭙﻠﻢ ﻳﺎ ﺑﺎﻻﺗﺮ ﺑﻪ ﺷﻜﻞ ﻣﻌﻨـﻲداري از ﻣﻴـﺰان
ﻫﻢﭼﻮن ﻣﻴﻜﺮوب ﺳﻞ ﺑﺎ درﮔﻴﺮي اﻧﺪامﻫﺎي ﻣﺨﺘﻠـﻒ و اﺷـﻜﺎل ﻣﺘﻨـﻮع
اﺑﺘﻼ ﻣﻲﻛﺎﺳﺖ .ﺑﻪﻋﺒﺎرﺗﻲ اﻓﺰاﻳﺶ ﺳﻄﺢ داﻧﺶ ﻣﺮدم ﺑﻪ وﻳﮋه روﺳـﺘﺎﻳﻴﺎن
ﺑﺎﻟﻴﻨﻲ ﺗﻈـﺎﻫﺮ ﻛﻨﻨـﺪ و دﻗـﺖ ﭘﺰﺷـﻚ ﻣﻮﺟـﺐ ﺗـﺸﺨﻴﺺ ﺑـﻪ ﻣﻮﻗـﻊ و
ﻣﻲﺗﻮاﻧﺪ ﻳﻜﻲ از روشﻫﺎي ﻣﺤﺎﻓﻈﺘﻲ ﻣﻔﻴﺪ در ﺑﺮاﺑﺮ اﻳﻦ ﺑﻴﻤﺎري ﺑﺎﺷـﺪ.
ﭘﻴﺸﮕﻴﺮي از ﻋﻮد و ﻋﻮارض ﺧﻮاﻫﺪ ﺷﺪ .ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺗﻨﻮع ﻋﻼﻳﻢ ﺑﺎﻟﻴﻨﻲ
از ﻧﻈﺮ ﻋﻼﻳﻢ ﺑﺎﻟﻴﻨﻲ ،ﺷﺎﻳﻊﺗﺮﻳﻦ ﻧﺸﺎﻧﻪ ﺑﺎﻟﻴﻨﻲ ﺗﺐ ،درد ﻣﻔﺎﺻﻞ ،ﺗﻌﺮﻳـﻖ،
ﻻزم اﺳﺖ در ﻫﺮ ﺑﻴﻤﺎر ﺗﺐ دار ﻃﻮل ﻛﺸﻴﺪه و ﻳﺎ ﺗﺐ ﺑﻪ ﻫﻤـﺮاه ﻋﻼﻳـﻢ
ﺿﻌﻒ و ﺑﻲﺣﺎﻟﻲ ﺑﻮده اﺳﺖ ﻛﻪ اﻳﻦ ﻳﺎﻓﺘـﻪﻫـﺎ ﺑـﺎ ﻧﺘـﺎﻳﺞ 23Haddadiدر
درﮔﻴﺮي اﻧﺪامﻫﺎي ﻣﺨﺘﻠﻒ ﺑﻪ وﻳﮋه ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ اﻧﺪﻣﻴﻚ ﺑﻮدن ﺑﺮوﺳـﻠﻮز
اﻳﺮان ﻫﻢﺧﻮاﻧﻲ داﺷﺖ اﻣﺎ ﺑﺎ ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮ ﻛﻤﻲ ﺗﻔﺎوت داﺷـﺖ ﺑـﺮاي
در اﻳﺮان ،اﻳﻦ ﺑﻴﻤﺎري در ﺗﺸﺨﻴﺺﻫﺎي اﻓﺘﺮاﻗﻲ ﻗﺮار ﮔﻴﺮد.
ﻣﺜﺎل در ﺑﺮرﺳﻲ 18Roushanﺷﺎﻳﻊﺗﺮﻳﻦ ﻧﺸﺎﻧﻪﻫﺎ ﺗﻌﺮﻳﻖ ،ﺗﺐ و آرﺗﺮاﻟﮋي
ﺳﭙﺎﺳﮕﺰاري :اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﭘﺎﻳﺎنﻧﺎﻣـﻪ ﺗﺤـﺖ ﻋﻨـﻮان "ﺑﺮرﺳـﻲ
ﺑﻮد اﻣﺎ 17Malikدر ﻋﺮﺑﺴﺘﺎن ،ﺗﺐ ،ﺗﻌﺮﻳـﻖ ،درد اﺳـﺘﺨﻮان ،ﻛﻤـﺮدرد و
ﺗﻈﺎﻫﺮات ﺑﺎﻟﻴﻨﻲ ،آزﻣﺎﻳﺸﮕﺎﻫﻲ و اﭘﻴﺪﻣﻴﻮﻟﻮژﻳﻚ ﺑﻴﻤﺎران ﻣﺒـﺘﻼ ﺑـﻪ ﺗـﺐ
ﺳﺮدرد را ﺷﺎﻳﻊﺗﺮﻳﻦ ﻧﺸﺎﻧﻪﻫﺎ ﻳﺎﻓﺘﻨـﺪ و 25Mousaﺗـﺐ ،ﻟـﺮز ،ﺗﻌﺮﻳـﻖ و
ﻣﺎﻟﺖ ﺑﺴﺘﺮي در ﺑﻴﻤﺎرﺳـﺘﺎن ﻓﺮﺷـﭽﻴﺎن ﺷـﻬﺮ ﻫﻤـﺪان ﻃـﻲ ﺳـﺎلﻫـﺎي
ﺳﺮدرد را ﺷﺎﻳﻊﺗﺮﻳﻦ ﻧﺸﺎﻧﻪﻫﺎ ﮔﺰارش ﻛﺮدﻧـﺪ .اﭘﻴﺪﻳـﺪﻳﻤﻮاورﻛﻴﺖ ﻳـﻚ
"1384-88در ﻣﻘﻄـــﻊ دﻛﺘـــﺮاي ﭘﺰﺷـــﻜﻲ در ﺳـــﺎل 1389و ﻛـــﺪ
ﻃﺮﻓﻪ ،ﻳﻜﻲ از ﺷﺎﻳﻊﺗﺮﻳﻦ ﻋﻮارض ادراري ﺗﻨﺎﺳﻠﻲ ﺑﺮوﺳـﻠﻮز اﺳـﺖ ﻛـﻪ
16/70/35552ﻣﻲﺑﺎﺷـﺪ ﻛـﻪ ﺑـﺎ ﺣﻤﺎﻳـﺖ داﻧـﺸﮕﺎه ﻋﻠـﻮم ﭘﺰﺷـﻜﻲ و
در اﻏﻠﺐ ﻣﻮارد ﺑﺎﻋﺚ اﻳﺠﺎد درد و ﺗﻮرم ﻣﻮﺿـﻌﻲ ﻫﻤـﺮاه ﺑـﺎ دﻳـﺰوري
ﺧﺪﻣﺎت ﺑﻬﺪاﺷﺘﻲ درﻣﺎﻧﻲ ﻫﻤﺪان اﺟﺮا ﺷﺪه اﺳﺖ.
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Edward J. Young brucellosis. In: Mandell GL, Bennett JE, Dolin R, editors. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia: Elsevier Churchill Livingstone Inc.; 2010. p. 2921-5. Corbel MJ, Beeching NJ. Brucellosis. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson L, et al, editors.
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ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
Epidemiological And clinical study of brucellosis in 230 patients
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Hall WH. Modern chemotherapy for brucellosis in humans. Rev Infect Dis 1990;12(6):1060-99. Hajia M, Keramat F. Study on the rate of Brucellosis relapse and efficiency different treatment protocols in among hospitalized patients in educational hospital of Hamadan. Military Med 2004;3:195-9. Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M, et al. Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore) 1996;75(4):195-211. Colmenero JD, Reguera JM, Fernández-Nebro A, CabreraFranquelo F. Osteoarticular complications of brucellosis. Ann Rheum Dis 1991;50(1):23-6. Alp E, Doganay M. Current therapeutic strategy in spinal brucellosis. Int J Infect Dis 2008;12(6):573-7. Schutze GE, Richard F. Brucellosis. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 17th ed. Philadelpha, PA: WB Saunders Co.; 2004. p. 939-41. Salata RA. Brucellosis. In: Goldman L, Schafer AI, editors. Goldman's Cecil Medicine. Philadelphia, PA: Saunders Elsevier; 2012. p. 1891-3. Annual Report of Center for Disease Control of Ministry of Health and Medical Education. 2004. [Persian] Maleknejad P, Peeri-DoGaheh H, AmirZargar A, Jafari S, Fatollahzadeh B. Diagnosis of brucellosis by use of BACTEC blood culture and confirmation by PCR. J Vet Res 2007;62(4):83-6. Dames S, Tonnerre C, Saint S, Jones SR. Clinical problemsolving. Don't know much about history. N Engl J Med 2005;352(22):2338-42. Mantur BG, Biradar MS, Bidri RC, Mulimani MS, Veerappa, Kariholu P, et al. Protean clinical manifestations and diagnostic challenges of human brucellosis in adults: 16 years' experience in an endemic area. J Med Microbiol 2006;55(Pt 7):897-903.
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16. Mantur BG, Mulimani MS, Bidari LH, Akki AS, Tikare NV. Bacteremia is as unpredictable as clinical manifestations in human brucellosis. Int J Infect Dis 2008;12(3):303-7. 17. Malik GM. A clinical study of brucellosis in adults in the Asir region of southern Saudi Arabia. Am J Trop Med Hyg 1997;56(4):375-7. 18. Hasanjani Roushan MR, Mohrez M, Smailnejad Gangi SM, Soleimani Amiri MJ, Hajiahmadi M. Epidemiological features and clinical manifestations in 469 adult patients with brucellosis in Babol, Northern Iran. Epidemiol Infect 2004;132(6):1109-14. 19. Serra Alvarez J, Godoy García P. Incidence, etiology and epidemiology of brucellosis in a rural area of the province of Lleida. Rev Esp Salud Publica 2000;74(1):45-53. 20. Elbeltagy KE. An epidemiological profile of brucellosis in Tabuk Province, Saudi Arabia. East Mediterr Health J 2001;7(4-5):791-8. 21. Haj Abdolbaghi M, Rasooli Nejad M, Yaghoob Zadeh M, Looti Shahrokhi B. Epidemiological, clinical, diagnostic and therapeutic survey in 505 cases with Brucellosis. Tehran Univ Med J (TUMJ) 2001;59(4):34-46. 22. Tasbakan MI, Yamazhan T, Gokengin D, Arda B, Sertpolat M, Ulusoy S, et al. Brucellosis: a retrospective evaluation. Trop Doct 2003;33(3):151-3. 23. Haddadi A, Rasoulinejad M, Afhami SH, Mohraz M. Epidemiological, clinical, para clinical aspects of brucellosis in Imam Khomeini and Sina Hospital of Tehran (1998-2005). Behbood J 2006;10(3):242-51. 24. Tohmé A, Hammoud A, el Rassi B, Germanos-Haddad M, Ghayad E. Human brucellosis. Retrospective studies of 63 cases in Lebanon. Presse Med 2001;30(27):1339-43. 25. Mousa AR, Elhag KM, Khogali M, Marafie AA. The nature of human brucellosis in Kuwait: study of 379 cases. Rev Infect Dis 1988;10(1):211-7. 26. Namiduru M, Gungor K, Dikensoy O, Baydar I, Ekinci E, Karaoglan I, et al. Epidemiological, clinical and laboratory features of brucellosis: a prospective evaluation of 120 adult patients. Int J Clin Pract 2003;57(1):20-4.
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺗﺸﺨﻴﺺ روش ﭘﺎﻳﺶ ﻛﺎراﻳﻲ Tehran University Medical Journal; Vol. 70, No.ﺑﺮاي 2, May 2012:دو130-135
A retrospective evaluation of epidemiological, clinical and laboratory features of brucellosis in 230 patients in Hamadan, Iran: a brief report
Abstract Peyman Eini M.D.1 Farzaneh Esna-Ashari M.D.2 Ahmad Reza Mobaien M.D.3* Mehdi Hasanzadeh M.D.4 1- Department of Infectious Diseases, Hamadan University of Medical Sciences, Hamadan, Iran. 2- Department of Community Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. 3- Department of Infectious Diseases, Zanjan University of Medical Sciences, Zanjan, Iran. 4- Clinical Research Center of Farshchian, Hamadan University of Medical Sciences, Hamadan, Iran.
Received: December 21, 2011 Accepted: January 23, 2012
Background: Brucellosis is one of the most common infectious diseases in Iran with very different clinical manifestations. Methods: In this retrospective descriptive study, all patients with brucellosis, who were admitted in Farshchian Hospital in Hamadan, Iran in 2005 to 2010, were enrolled in the study. The data were collected from the patients’ medical records and were entered in forms for analysis. Results: A total of 230 patients with brucellosis, including 130 (56.5%) male and 100 (43.5%) female patients with a mean age of 40.84±20.29 years, who mostly (72.2%) lived
in rural areas were enrolled in the study. Outbreaks were most common in spring and summer and the main route of transmission was consumption of contaminated dairy products (60.3%). The most common symptoms were fever (77.4%), arthralgia (70%), sweating (47%), malaise and fatigue (46.5%). Arthritis and epididymo- orchitis were seen in 121 (52.9%) and 48 (8.20%) patients, respectively. CBC analysis showed leukocytosis in 20.8% of the participants. ESR rise was noted in 59.5% of the patients and 52.9% had positive CRP. Conclusion: Given to various clinical presentations, brucellosis should be considered in the differential diagnosis of individuals with chronic fever with or without other organ abnormalities. Keywords: Brucellosis, clinical, epidemiology, laboratory, manifestation, serologic test.
*
Corresponding author: Department Of Infectious Diseases, Valiasr Hospital, Fazlolah Ave., Zanjan, Iran. Tel: +98- 241- 7123303 E-mail: amobaien@yahoo.com
1391 اردﻳﺒﻬﺸﺖ،2 ﺷﻤﺎره،70 دوره، داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان،ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ
ﻛﻠﻴﻪ اردﻳﺒﻬﺸﺖ 136-139 ،1391 ﺷﻤﺎره ،2 در دوره ﺗﻬﺮان، ﭘﻠﻲﭘﺰﺷﻜﻲ ﻋﻠﻮم داﻧﺸﮕﺎه ﭘﺰﺷﻜﻲ، آﻧﺘﻲﺑﺎديﻣﺠﻠﻪ ، 70ﻣﺰﻣﻦ ﻧﺎرﺳﺎﻳﻲ ﺳﺎﻛﺎرﻳﺪي واﻛﺴﻦ ﺗﺰرﻳﻖ داﻧﺸﻜﺪهﺑﻌﺪ از اﺧﺘﺼﺎﺻﻲ
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درﻣﺎن ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ واﺑﺴﺘﻪ ﺑﻪ اﻳﺪز :ﮔﺰارش ﻣﻮردي
ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ﻣﻘﺎﻟﻪ 1390/05/15 :ﺗﺎرﻳﺦ ﭘﺬﻳﺮش1390/11/01 :
ﭼﻜﻴﺪه
زﻫﺮا ﻋﺒﺪي *
ﻧﺪا ﻋﻠﻴﺠﺎﻧﻲ
زﻣﻴﻨﻪ و ﻫﺪف :ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ در ﺑﻴﻤﺎران اﻳﺪز دﻳﺪه ﻣﻲﺷﻮد .ﻣﻴﺰان ﺑﺮوز ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ﺑﺎ اﻓﺰاﻳﺶ ﻧﻘﺺ اﻳﻤﻨﻲ اﻓﺰاﻳﺶ ﮔﺮوه ﻋﻔﻮﻧﻲ ،ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎمﺧﻤﻴﻨﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم
ﻣﻲﻳﺎﺑﺪ .ﻋﻠﺖ ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ در اﻳﺪز ﺑﻪ دو دﺳﺘﻪ اوﻟﻴﻪ و ﺛﺎﻧﻮﻳﻪ ﺗﻘﺴﻴﻢ ﻣﻲﺷﻮد .ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ اوﻟﻴﻪ ﺷﺎﻳﻊﺗـﺮﻳﻦ ﻋﻠـﺖ
ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،ﺗﻬﺮان ،اﻳﺮان.
ﻛﺎﻫﺶ ﭘﻼﻛﺖ در اﻳﺪز ﻣﻲﺑﺎﺷﺪ .ﻣﻌﺮﻓﻲ ﺑﻴﻤﺎر :ﺑﻴﻤﺎر آﻗﺎي 35ﺳﺎﻟﻪ ﻣﻮرد اﻳـﺪز از ﺳـﺎل 1375ﻛـﻪ ﺑـﺎ ﭘﺘـﺸﻲ ،ﭘﻮرﭘـﻮرا، اﻛﻴﻤﻮز در اﻃﺮاف ﭼﺸﻢ و اﻧﺪامﻫﺎ و ﺧﻮنرﻳﺰي ﻣﻠﺘﺤﻤﻪ ﭼﺸﻢ در ﺷﻬﺮﻳﻮر ﻣﺎه 1389در ﺑﺨﺶ ﻋﻔﻮﻧﻲ ﺑﻴﻤﺎرﺳـﺘﺎن اﻣـﺎم ﺧﻤﻴﻨﻲ )ره( ﺑﺴﺘﺮي ﺷﺪه اﺳﺖ .در ﺑﺮرﺳﻲ ﭘﻼﻛﺖ ﺑﻴﻤﺎر 5000cu/mmﺑﻮد و ﺑﻌـﺪ از رد ﻋﻠـﻞ ﺛﺎﻧﻮﻳـﻪ ﺗﺮوﻣﺒﻮﺳـﻴﺘﻮﭘﻨﻲ، ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ اوﻟﻴﻪ ﻣﻄﺮح ﺷﺪ و ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ﺷﺪﻳﺪ و ﻋﻼﻳﻢ ﺧـﻮنرﻳـﺰي و ﺗﻮﺟـﻪ ﺑـﻪ اﻳـﻦ ﻧﻜﺘـﻪ ﻛـﻪ زﻳﺪوودﻳﻦ و ﺳﺎﻳﺮ داروﻫﺎي ﺿﺪ رﺗﺮووﻳﺮوﺳﻲ ﺟﻬﺖ ﺗﺄﺛﻴﺮ 4-6ﻫﻔﺘﻪ زﻣﺎن ﻧﻴﺎز دارﻧﺪ ،ﺟﻬﺖ ﺑﻴﻤﺎر ﭘﺮدﻧﻴﺰون ﺑﻪ ﻫﻤـﺮاه آﻧﺘﻲرﺗﺮوواﻳﺮال ﺷﺮوع ﺷﺪ .ﺑﻌﺪ از ﺣﺪود دو ﻫﻔﺘﻪ از ﺷﺮوع ﻛﻮرﺗﻮن ﭘﻼﻛﺖ ﺑﻪ ﺣـﺪود 50000cu/mmرﺳـﻴﺪ و ﺑﻌـﺪ از ﻫﺸﺖ ﻫﻔﺘﻪ از ﻣﺼﺮف آﻧﺘﻲ رﺗﺮوواﻳﺮال )زﻳﺪوودﻳﻦ( ﭘﻼﻛﺖ ﺑﻪ ﺣﺪود 140000cu/mmرﺳﻴﺪ .ﻧﺘﻴﺠـﻪ ﮔﻴـﺮي :ﺑـﻪ ﻧﻈـﺮ ﻣﻲرﺳﺪ در درﻣﺎن ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ اوﻟﻴﻪ در ﺑﻴﻤﺎران HIVدر ﺻﻮرت ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ﺷﺪﻳﺪ و ﻋﻼﻳﻢ ﺧﻮنرﻳﺰي ﻣﻲﺗـﻮان
*
ﻧﻮﻳﺴﻨﺪه ﻣﺴﺌﻮل :ﺗﻬﺮان ،ﺑﻠﻮار ﻛﺸﺎورز ،ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎم
ﺧﻤﻴﻨﻲ
از ﭘﺮدﻧﻴﺰون ﺑﻪ ﻫﻤﺮاه آﻧﺘﻲرﺗﺮوواﻳﺮال اﺳﺘﻔﺎده ﻛﺮد.
ﺗﻠﻔﻦ021-61192811 : E-mail: dna1461@yahoo.com
ﻛﻠﻤﺎت ﻛﻠﻴﺪي :اﻳﺪز ،ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ،درﻣﺎن آﻧﺘﻲرﺗﺮوواﻳﺮال.
ﻣﻘﺪﻣﻪ
HIVﻛﻨﺘﺮل ﻧﺸﺪه و ﻋﻔﻮﻧﺖ ﻫﻢزﻣﺎن ﻫﭙﺎﺗﻴﺖ cدﻳﺪه ﻣـﻲﺷـﻮد 4.ﻋﻠـﺖ ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ در اﻳﺪز ﺑﻪ دو دﺳﺘﻪ اوﻟﻴـﻪ و ﺛﺎﻧﻮﻳـﻪ ﺗﻘـﺴﻴﻢ ﻣـﻲﺷـﻮد.
ﺗﺮوﻣﺒﻮﺳــﻴﺘﻮﭘﻨﻲ ) (Thrombocytopeniaدر ﺑﻴﻤــﺎران اﻳــﺪز دﻳــﺪه
ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ اوﻟﻴﻪ
Primary HIV Associated Thrombocytopenia
ﻣﻲﺷﻮد .در ﻳﻚ ﻣﻄﺎﻟﻌﻪ در ﺑﻴﻤﺎران اﻳـﺪز ،آﻧﻤـﻲ در ،%70ﻟﻨﻔـﻮﭘﻨﻲ در
) (PHATﺷﺎﻳﻊﺗﺮﻳﻦ ﻋﻠﺖ ﻛـﺎﻫﺶ ﭘﻼﻛـﺖ در اﻳـﺪز ﻣـﻲﺑﺎﺷـﺪ .از ﻧﻈـﺮ
،%70ﻧﻮﺗﺮوﭘﻨﻲ در %50و ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ در %40ﻣﻮارد ﮔﺰارش ﺷـﺪه
ﻛﻠﻴﻨﻴﻜــﻲ ﺗﺮوﻣﺒﻮﺳــﻴﺘﻮﭘﻨﻲ اوﻟﻴــﻪ ﺷــﺒﻴﻪ ﭘﻮرﭘــﻮراي ﺗﺮوﻣﺒﻮﺳــﻴﺘﻮﭘﻨﻲ
اﺳﺖ 1.ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ واﺑﺴﺘﻪ ﺑﻪ اﻳﺪز در ﺑﻴﻤﺎران ﺑﺎ رﻳﺴﻚ ﺑـﺎﻻ ﺷـﺎﻣﻞ
اﻳﺪﻳﻮﭘﺎﺗﻴﻚ
اﻓﺮادي ﻛﻪ از ﻃﺮﻳﻖ ﻫﻤﻮﺳﻜﺴﻮال ،ﻫﺘﺮوﺳﻜﺴﻮال ،ﻣﺼﺮف ﻣﻮاد ﻣﺨـﺪر
وﻟﻲ اﺳﭙﻠﻨﻮﻣﮕﺎﻟﻲ ﺑﻴﺶﺗﺮ از ITPدﻳﺪه ﻣﻲﺷﻮد و ﻣﻴﺰان ﭘﻼﻛﺖ ﺑـﻴﺶﺗـﺮ
ﺗﺰرﻳﻘﻲ ،ﺗﺰرﻳﻖ ﺧﻮن ﻣﺒﺘﻼ ﺷﺪهاﻧﺪ ،اﺗﻔﺎق ﻣﻲاﻓﺘﺪ .ﻣﻴﺰان ﺑﺮوز ﺗﺮوﻣﺒـﻮ-
از ITPﻣﻲﺑﺎﺷﺪ 5-7.ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ﺛﺎﻧﻮﻳﻪ ﺑﻪ ﻋﻠﺖ ﻋﻔﻮﻧﺖﻫﺎي ﻓﺮﺻـﺖ
ﺳﻴﺘﻮﭘﻨﻲ ﺑﺎ اﻓﺰاﻳﺶ ﻧﻘﺺ اﻳﻤﻨﻲ اﻓﺰاﻳﺶ ﻣﻲﻳﺎﺑﺪ .در ﻳﻚ ﻣﻄﺎﻟﻌـﻪ ﺑـﺮوز
)(ITP
Idiopathic Thrombocytopenic Purpuraﻣﻲﺑﺎﺷـﺪ
8
ﻃﻠﺐ ،ﻫﺎﻳﭙﺮاﺳﭙﻠﻨﻴﺴﻢ و ﻋﻮارض داروﻳﻲ ﻣﻲﺑﺎﺷﺪ.
ﭘﻼﻛﺖ زﻳﺮ %8 ،150000cu/mmدر ﺑﻴﻤﺎران ﺑـﺎ %30 ،200-500 CD4 در ﺑﻴﻤﺎران ﺑﺎ CD4ﻛﻢﺗﺮ از 200ﮔﺰارش ﺷﺪه اﺳـﺖ 2.ﺗﺮوﻣﺒﻮﺳـﻴﺘﻮﭘﻨﻲ ﻣﻤﻜﻦ اﺳﺖ اوﻟﻴﻦ ﻋﻼﻣﺖ اﻳﺪز در %10ﺑﻴﻤﺎران ﺑﺎﺷﺪ 3.از زﻣﺎن اﺳﺘﻔﺎده داروﻫـﺎي ﺿـﺪ رﺗﺮووﻳﺮوﺳـﻲ ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨـﻲ ﺑﻴـﺶﺗﺮ در ﺑﻴﻤـﺎران ﺑﺎ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻣﻌﺮﻓﻲ ﺑﻴﻤﺎر ﺑﻴﻤـﺎر آﻗـﺎي 35ﺳﺎﻟﻪ ﻣﻮرد اﻳﺪز از ﺳﺎل 75ﻛﻪ ﺑﺎ ﭘﺘﺸﻲ ،ﭘﻮرﭘﻮرا،
زﻫﺮا ﻋﺒﺪي و ﻫﻤﻜﺎران
137
ﺟﺪول :1 -روﻧﺪ ﭘﻼﻛﺖ ﺑﻴﻤﺎر CBC / date
89/5/31
89/6/3
89/6/13
89/7/6
89/8/19
WBC
5/4
6/9
8
11/2
6/3
Hb
8/8
11/2
10/2
10/5
11/3
Mcv
84/6
84/1
88/8
92/5
93/3
5
6
22
54
140
Plt
اﻛﻴﻤﻮز در اﻃﺮاف ﭼﺸﻢ و اﻧﺪامﻫﺎ و ﺧﻮنرﻳﺰي ﻣﻠﺘﺤﻤﻪ ﭼﺸﻢ ﺷﻬﺮﻳﻮر
ﺳﻴﺘﻮﭘﻨﻲ اوﻟﻴﻪ ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﻣﻴﺰان ﭘﻼﻛﺖ را ﺑـﻴﺶﺗـﺮ از 50000cu/mm
ﻣﺎه 1389در ﺑﺨﺶ ﻋﻔﻮﻧﻲ ﺑﻴﻤﺎرﺳﺘﺎن اﻣـﺎمﺧﻤﻴﻨـﻲ )ره( ﺑـﺴﺘﺮي ﺷـﺪه
ﺑﻌﺪ از ﻫﺸﺖ ﻫﻔﺘﻪ درﻣـﺎن اﻓـﺰاﻳﺶ ﻣـﻲدﻫـﺪ 9.در اﺑﺘـﺪا زﻳـﺪودﻳﻦ ﺑـﺎ
اﺳﺖ .ﺑﻴﻤﺎر ﺳﺎﺑﻘﻪ ﻧﺎرﺳﺎﻳﻲ ﺣﺎد ﻛﻠﻴﻪ در ﺳﺎل 74را ﻣﻲدﻫﺪ ﻛﻪ ﭼﻨﺪﻳﻦ
دوز 600mg/dayآﻏﺎز ﻣﻲﺷﻮد و در ﺻـﻮرﺗﻲ ﻛـﻪ ﺑﻌـﺪ از 4-8ﻫﻔﺘـﻪ
ﻧﻮﺑﺖ ﻫﻤﻮدﻳﺎﻟﻴﺰ ﺷﺪه اﺳﺖ ﻫﻢﭼﻨﻴﻦ ﺑﻪ ﻣﺪت ﭼﻬﺎر ﺳﺎل ﻗﺒـﻞ از ﺳـﺎل
ﺗﻐﻴﻴﺮي در ﺗﻌﺪاد ﭘﻼﻛﺖ اﻳﺠﺎد ﻧﺸﻮد دوز آن ﺑـﻪ 1000-1500mg/day 10
،75ﻣــﺼﺮف ﻣــﻮاد ﻣﺨــﺪر ﺗﺰرﻳﻘ ـﻲ داﺷــﺘﻪ اﺳــﺖ .در ﻣﻌﺎﻳﻨــﻪ اوﻟﻴــﻪ،
اﻓﺰاﻳﺶ ﻣـﻲﻳﺎﺑـﺪ .اﺳـﺘﻔﺎده از درﻣـﺎنﻫـﺎي اﺿـﺎﻓﻲ ﺑـﺴﺘﻪ ﺑـﻪ ﺷـﺪت
،RR:18/min ،OT:37 ºC ،PR:80/min ،BP:120/80mmHgﻣﻠﺘﺤﻤـــــﻪ
ﺗﺮوﻣﺒﻮﺳــﻴﺘﻮﭘﻨﻲ ،ﻋﻼﻳــﻢ ﺧــﻮنرﻳــﺰي ﻣﺎﻧﻨــﺪ ﭘﺘــﺸﻲ ،اﭘﻴﺴﺘﺎﻛــﺴﻲ و
رﻧﮓ ﭘﺮﻳﺪه ،ﺧﻮنرﻳﺰي در ﻣﻠﺘﺤﻤﻪ ،ﭘﺘﺸﻲ در اﻃﺮاف ﭼﺸﻢﻫـﺎ ،ﭘﺘـﺸﻲ،
ﻫﻤﺎﭼﻮري و ﺷﺮاﻳﻂ ﻫﻤﺮاه ﻣﺎﻧﻨﺪ ﻛﻤﺒﻮد ﻓﺎﻛﺘﻮرﻫﺎي اﻧﻌﻘﺎدي ﻣـﻲﺑﺎﺷـﺪ.
ﭘﻮرﭘﻮرا ،اﻛﻴﻤﻮز در اﻧﺪامﻫﺎ داﺷـﺘﻪ اﺳـﺖ و در ﻣﻌﺎﻳﻨـﻪ اﻓﺘﺎﻟﻤﻮﺳـﻜﻮﭘﻲ
از درﻣﺎنﻫﺎي ﻣﺘﺪاول اﺳﺘﻔﺎده از اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻮﻟﻴﻦ داﺧﻞ ورﻳـﺪي
ﺧﻮنرﻳﺰي در اﻳﻨﻔﺮاﺗﻤﭙﻮرال ﺷﺒﻜﻴﻪ داﺷﺘﻪ اﺳﺖ ،وﻟﻲ ﺷﻮاﻫﺪي ﺑﻪ ﻧﻔـﻊ
ﻣﻲﺑﺎﺷﺪ ﻛﻪ اﻓﺰاﻳﺶ دراﻣﺎﺗﻴﻚ در ﺗﻌﺪاد ﭘﻼﻛـﺖﻫـﺎ اﻳﺠـﺎد ﻣـﻲﻛﻨـﺪ در
ﻋﻔﻮﻧﺖﻫﺎي ﻓﺮﺻﺖ ﻃﻠﺐ ﻧﺪاﺷﺖ .در آزﻣﺎﻳﺸﺎت اﻧﺠـﺎم ﺷـﺪه ﻗﺒـﻞ از
ﻣﻄﺎﻟﻌﻪاي اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻮﻟﻴﻦ داﺧـﻞ ورﻳـﺪي اﻓـﺰاﻳﺶ 50000cu/mmدر
)(IVIG
11
ﺑﺴﺘﺮي HBS Ag, HBC Ab ، Ab، HCV Ab :ﻣﺜﺒﺖ و آﺧﺮﻳﻦ CD4ﺑﻴﻤﺎر
%90ﺑﻴﻤﺎران ﺑﻌﺪ از ﺗﺠﻮﻳﺰ دوز واﺣﺪ داﺷﺘﻪ اﺳﺖ .اﺛﺮ آن ﮔﺬار ﺑـﻮده
در ﺗــﺎرﻳﺦ ،VDRL ،95 ،89/5/27آﻧﺘــﻲﺗﻮﻛــﺴﻮﭘﻼﺳﻤﺎ آﻧﺘــﻲﺑــﺎدي،
و ﺑﻪ ﺗﻜﺮار ﺗﺠﻮﻳﺰ ﻣﺘﻌﺪد ﻧﻴﺎزﻣﻨﺪ اﺳﺖ 12.ﻋﻼوه ﺑﺮ آن ﻗﻴﻤﺖ ﺑﺎﻻ ،ﻣﺪت
آﻧﺘﻲﺳﺎﻳﺘﻮﻣﮕﺎﻟﻮوﻳﺮوس آﻧﺘﻲﺑﺎدي ﻣﻨﻔﻲ ﺑﻮده اﺳﺖ آزﻣﺎﻳﺶ CBDﺑﻴﻤﺎر
ﻃﻮﻻﻧﻲ اﻧﻔﻮزﻳﻮن ) 4-5ﺳﺎﻋﺖ( و ﻛﻤﺒﻮد اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻮﻟﻴﻦﻫـﺎي اﻧـﺴﺎﻧﻲ
در ﺗﺎرﻳﺦ ،Mcv=84/6fl ،Hb=8/8mg/dl ،WBC=5/4cu/mm :89/5/31
ﻣﻮﺟﺐ ﻣﺤﺪودﻳﺖ اﺳﺘﻔﺎده از آن ﻣﻲﺷﻮد .اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻴﻦ داﺧﻞ ورﻳﺪي
Plt=5×103cu/mmﺑــﻮده اﺳــﺖ .ﺑــﺎ ﺗﻮﺟــﻪ ﺑــﻪ ﺑــﺎي ﺳــﻴﺘﻮﭘﻨﻲ ﺑﻴﻤــﺎر
درﻣــﺎن اﻧﺘﺨــﺎﺑﻲ در ﻣــﻮاردي اﺳــﺖ ﻛــﻪ ﻧﻴــﺎز ﺑــﻪ اﺻــﻼح ﺳــﺮﻳﻊ
آﺳﭙﻴﺮاﺳﻴﻮن و ﺑﻴﻮﭘﺴﻲ ﻣﻐـﺰ اﺳـﺘﺨﻮان اﻧﺠـﺎم ﺷـﺪ ﻛـﻪ ﻫـﺎﻳﭙﺮﭘﻼزي و
ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ وﺟﻮد دارد 13.درﻣﺎن دﻳﮕﺮ روﮔﺎم ) Anti Rh (Dﻣﻲﺑﺎﺷﺪ
دﻳﺴﭙﻼﺳﺘﻴﻚ ﮔﺮاﻧﻮﻟﻮﺳﻴﺖ و ﻣﮕﺎﻛﺎرﻳﻮﺳﻴﺖ ﮔﺰارش ﺷﺪ .ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ
و در ﺑﻴﻤﺎراﻧﻲ ﻛﻪ اﺳﭙﻠﻨﻜﺘﻮﻣﻲ ﻧﺸﺪهاﻧـﺪ و Rhﻣﺜﺒـﺖ ﻣـﻲﺑﺎﺷـﻨﺪ ﻣـﺆﺛﺮ
رد ﻋﻠﻞ ﺛﺎﻧﻮﻳﻪ ﺗﺮوﻣﺒﻮﺳﻴﺘﻮﭘﻨﻲ ﺗﺸﺨﻴﺺ ﺗﺮوﻣﺒﻮﺳـﻴﺘﻮﭘﻨﻲ اوﻟﻴـﻪ ﻣﻄـﺮح
14
اﺳﺖ.
روﮔﺎم ) Anti Rh (Dارزانﺗﺮ از اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻴﻦ داﺧﻞ ورﻳﺪي اﺳـﺖ
ﺷﺪ و ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ CD4ﺑﻴﻤـﺎر و ﺗﺮوﻣﺒﻮﺳـﻴﺘﻮﭘﻨﻲ از ﺗـﺎرﻳﺦ 89/6/16 ﺗﺤﺖ درﻣﺎن آﻧﺘﻲرﺗﺮوواﻳﺮال ﻗﺮار ﮔﺮﻓﺖ و ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﺗﺮوﻣﺒﻮﺳـﻴﺘﻮﭘﻨﻲ
و ﻣﺪت اﻧﻔﻮزﻳﻮن آن ﻛﻢﺗﺮ ﻣﻲﺑﺎﺷﺪ )ﻛﻢﺗﺮ از ﭘﻨﺞ دﻗﻴﻘﻪ( 15.روﮔﺎم
Anti
Rhﻣﻮﺟﺐ ﻛﺎﻫﺶ ﻫﻤﻮﮔﻠﻮﺑﻴﻦ ﺣﺪود 0/5-2gr/dlﻣﻲﺷﻮد و ﺑﺎﻳـﺪ
ﺷﺪﻳﺪ و ﻋﻼﻳﻢ ﺧﻮنرﻳﺰي ﺗﺤـﺖ درﻣـﺎن ﺑـﺎ ﭘﺮدﻧﻴـﺰون 1mg/kgﻗـﺮار
)(D
ﮔﺮﻓﺖ .در ﺟﺪول 1ﻧﺘﺎﻳﺞ CBCﺑﻴﻤﺎر ﺧﻼﺻﻪ ﺷﺪه اﺳﺖ.
در ﺑﻴﻤﺎران دﭼﺎر ﻛﻢ ﺧﻮﻧﻲ ﺑﺎ اﺣﺘﻴﺎط ﺑﻪ ﻛـﺎر ﮔﺮﻓﺘـﻪ ﺷـﻮد .ﺗﻜـﺮار دوز 17و16
ﻣﻌﻤﻮﻻ 3-4ﻫﻔﺘﻪ ﺑﻌﺪ از دوز اوﻟﻴﻪ ﻻزم ﻣـﻲﺷـﻮد.
ﺑﺤﺚ
از درﻣـﺎنﻫـﺎي
دﻳﮕﺮ ﻛﻮرﺗﻴﻜﻮاﺳﺘﺮوﻳﻴﺪ )ﭘﺮدﻧﻴﺰون (1mg/kg/dﻣﻲﺑﺎﺷﺪ ﻛـﻪ ﺑـﻪ ﻋﻠـﺖ اﻓﺰاﻳﺶ ﻋﻔﻮﻧﺖﻫﺎي ﻓﺮﺻﺖ ﻃﻠﺐ در ﻣﺪت ﻛﻮﺗﺎه اﺳﺘﻔﺎده ﻣـﻲﺷـﻮد در
زﻳﺪوودﻳﻦ ) (Zidovudineﻳﻜـﻲ از درﻣـﺎنﻫﺎي اﺻﻠـﻲ ﺗـﺮوﻣﺒـﻮ-
ﻳﻚ ﻣﻄﺎﻟﻌﻪ %80ﺑﻴﻤﺎران ﭘﺎﺳﺦ ﻣﻨﺎﺳﺐ ﺑﻪ ﻛﻮرﺗـﻮن دادهاﻧـﺪ و رﻳـﺴﻚ
ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ ،داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﺗﻬﺮان ،دوره ،70ﺷﻤﺎره ،2اردﻳﺒﻬﺸﺖ 1391
ﻳﻲ ﻣﺰﻣﻦ ﻛﻠﻴﻪAbdi ﻧﺎرﺳﺎZ.درetيal. آﻧﺘﻲﺑﺎدي اﺧﺘﺼﺎﺻﻲ ﺑﻌﺪ از ﺗﺰرﻳﻖ واﻛﺴﻦ ﭘﻠﻲﺳﺎﻛﺎرﻳﺪ
ﻧﻴﺎز ﺟﻬﺖ اﺛﺮ آﻧﺘﻲرﺗﺮوواﻳﺮال ﻧﻴﺎز ﺑﻪ درﻣﺎن ﻛﻤﻜﻲ وﺟـﻮد داﺷـﺖ ﻛـﻪ
138
از درﻣـﺎنﻫـﺎي18.ﺧﻮنرﻳﺰي ﺑﻌﺪ از ﺳﻪ ﻫﻔﺘﻪ درﻣﺎن ﻛﺎﻫﺶ ﻳﺎﻓﺘﻪ اﺳﺖ
ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻋﺪم اﻣﻜﺎن اﺳﺘﻔﺎده از اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻴﻦ داﺧﻞ ورﻳﺪي ﺑﻪ ﻋﻠـﺖ
دﻳﮕﺮ در ﺑﻴﻤﺎراﻧﻲ ﻛﻪ ﺑﺎ درﻣﺎن آﻧﺘﻲرﺗﺮوواﻳﺮال ﺑﻪ ﺗﻨﻬـﺎﻳﻲ ﭘﺎﺳـﺦ ﻣـﺆﺛﺮ
ﭘـﺎﻳﻴﻦ در اﻳـﻦ ﺑﻴﻤـﺎر از ﭘﺮدﻧﻴـﺰونHb ﻗﻴﻤﺖ ﺑﺎﻻ و روﮔـﺎم ﺑـﻪ ﻋﻠـﺖ
19
. اﻳﻨﺘﺮﻓﺮون آﻟﻔﺎ و وﻳﻦﻛﺮﻳﺴﺘﻴﻦ ﻣﻲﺑﺎﺷـﺪ، داﭘﺴﻮن، داﻧﺎزول:ﻧﻤﻲدﻫﻨﺪ
ﺑﻌـﺪ از ﺣـﺪود دو ﻫﻔﺘـﻪ از. ﺑﻪ ﻣﺪت ﺳﻪ ﻫﻔﺘﻪ اﺳﺘﻔﺎده ﺷﺪ1mg/kg/d
در ﺻــﻮرﺗﻲ ﻛــﻪ ﺗﺮوﻣﺒﻮﺳــﻴﺘﻮﭘﻨﻲ ﻣﻘــﺎوم و واﺑــﺴﺘﻪ ﺑــﻪ ﺗﺠــﻮﻳﺰ ﻣﻜــﺮر
.(1 رﺳـﻴﺪ )ﺟـﺪول54000cu/mm ﺷﺮوع ﭘﺮدﻧﻴﺰون ﭘﻼﻛﺖ ﺑﻴﻤـﺎر ﺑـﻪ
ﺷﻮد ﻣﻤﻜـﻦ اﺳـﺖAnti Rh (D) اﻳﻤﻮﻧﻮﮔﻠﻮﺑﻴﻦ داﺧﻞ ورﻳﺪي ﻳﺎ روﮔﺎم
ﺧﻮنرﻳﺰي ﻣﻠﺘﺤﻤﻪ و ﺿـﺎﻳﻌﺎت ﭘﻮﺳـﺘﻲ رﻓـﻊ ﺷـﺪ و ﺑـﺎ درﻣـﺎن ﺿـﺪ
در ﺑﻴﻤﺎر ﻣﻌﺮﻓﻲ ﺷﺪه ﺑﺎ ﺗﻮﺟـﻪ ﺑـﻪ16.ﺑﻴﻤﺎران از اﺳﭙﻠﻨﻜﺘﻮﻣﻲ ﺳﻮد ﺑﺒﺮﻧﺪ
. رﺳﻴﺪ140000cu/mm رﺗﺮووﻳﺮوﺳﻲ ﺑﻌﺪ از ﻫﺸﺖ ﻫﻔﺘﻪ ﭘﻼﻛﺖ ﺑﻪ
ﭘﻼﻛﺖ ﺑﺴﻴﺎر ﭘﺎﻳﻴﻦ ﺑﻴﻤﺎر و ﻋﻼﻳﻢ ﺧﻮنرﻳﺰي و ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ زﻣﺎن ﻣـﻮرد
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ﻋﻤﻮﻣﻲ ﺑﺨﺸﻬﺎي ﺟﺮاﺣﻲ ﺟﺮاﺣﻲ در ﻋﻔﻮﻧﺖ ﻣﺤﻞ ﺗﺸﺨﻴﺺ ﭘﺎﻳﺶ2012: دو روش136-139 ﻛﺎراﻳﻲ Tehran University Medical Journal; Vol. 70, No.ﺑﺮاي 2, May
Treatment of AIDS-related thrombocytopenia: a case report
Abstract
Received: August 06, 2011 Accepted: January 21, 2012
Zahra Abdi M.D. Neda Alijani M.D.*
Background: Thrombocytopenia is a common finding in individuals infected with HIV Department of Infectious Disease Specialist, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
and its incidence increases with progressive immunosuppression. Thrombocytopenia due to AIDS is divided into primary and secondary forms and primary HIV associated thrombocytopenia (PHAT) is the most common cause of thrombocytopenia in these patients. Case presentation: The patient was a 35-year old man with HIV since 1996, who was admitted to Imam Khomeini hospital in August of 2010 with petechiae, purpura, ecchymosis around the eyes and on the limbs and subconjunctival hemorrhage. In laboratory investigation, platelet count was 5000/µL. After ruling out the secondary causes of thrombocytopenia, Primary HIV Associated Thrombocytopenia (PHAT) was diagnosed. Due to the presence of severe thrombocytopenia and bleeding symptoms and considering the fact that antiretroviral agents require 4- 6 weeks to reach therapeutic effects, prednisone and antiretrovirals (AZT) were prescribed. After about two weeks of steroids administration, platelet count reached 50,000/µL and about eight weeks after antiretroviral (AZT) therapy platelets reached nearly 140,000/µL. Conclusion: Prednisone can be used safely in conjunction with antiretrovirals for primary thrombocytopenia in HIV infected patients with severe thrombocytopenia and bleeding symptoms. Keywords: Antiretroviral, HIV, thrombocytopenia.
*
Corresponding author: Imam Khomeini Hospital, Blvd., Keshavarz Blvd., Tehran, Iran. Tel: +98- 21- 61192811 E-mail:dna1461@yahoo.com
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Textbook of Pain. 3rd ed. Edinburgh: Churchill Livingstone; 1994. p. 963-89.
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Tehran University Medical Journal Tehran University Medical Journal Volume64, 70Number Number 2 May2006 2012 Volume 8, November
Contents
Recipient kidney damage after leukocyte transfer from inbred mice with renal ischemia-reperfusion injury………………………..………………………………………….…............69 Kadkhodaee M, Khastar H, Seifi B, Najafi A, Delavari F.
Histopathological and histomorphometrical effects of atorvastatin on experimental femoral cortical bone defect healing in rats……………………………………...…...........78 Mousavi Gh, Mohajeri D, Rezaie A, Valilu M.R, Alimohamadi A.
TGF-b downregulation by RNAi technique in ex vivo-expanded HSCs on 3D DBM scaffold………............86 Hashemi Z. S, Forouzandeh Moghadam M, Soleimani M, Hafizi M, Amirizadeh N.
In vitro antifungal susceptibility of oral candida species from Iranian HIV infected patients…….............96 Katiraee F, Khosravi A.R, Khalaj V, Hajiabdolbaghi M, Khaksar A.A, Rasoulinejad M.
Biological plating in comminuted subtrochanteric fractures…................................................................104 Mehrpour S.R, Tavvafi M.R, Sorbi R, Aghamirsalim M.R.
Effects of resistance and endurance exercises on androgens, cortisol and lactate in elderly women…......................................................................................................................................110 Sourati Jabloo D, Attarzadeh Hosseini S. R, Sayadpour Zanjani D, Ahmadi A.
Intra- articular hyaluronic acid injections Vs. dextrose prolotherapy in the treatment of osteoarthritic knee pain…........................................................................................................................119 Hashemi S. M, Madadi F, Razavi S, Nikooseresht M, Hassanzadeh Kiyabi F, Nasiripour S.
Prevalence of colorectal polyps among women with ovarian and endometrial cancers admitted in Firoozgar, Akbarabadi and Rasol Akram Hospitals during 2010- 2011: a brief report…..……................126 Jafari S, Khaleghi S, Basi A, Ramim T.
A retrospective evaluation of epidemiological, clinical and laboratory features of brucellosis in 230 patients in Hamadan, Iran: a brief report….................................................................130 Eini P, Esna-Ashari F, Mobaien A.R, Hasanzadeh M.
Treatment of AIDS-related thrombocytopenia: a case report ….................................................................136 Abdi Z, Alijani N.
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TUMJ
TEHRAN UNIVERSITY MEDICAL JOURNAL The Official Publication of Medical School, Tehran University of Medical Sciences Volume 70
Number 2
May 2012
Chairman: S.H. Emami Razavi Editor in Chief: N. Behtash Executive Editor: M.A. Noyan Ashraf Associate Editors: SH. Akhondzadeh, A. Arab Kheradmand, N. Ataei, S. Borna, M. Ghazi Khansari, S.J. Ghazi Mirsaeed, J. Hajati, M. Kadkhodaei, A. Khoshnevisan, S. Moradmand, Z. Nadiya Hatmi, M.A. Noyan Ashraf, R. Omranipoor, N. Rezaei, N. Sajjadian Editorial Board: M. Akbarian, F. AmoozegarHashemi, B. Bahar, F. Davari Tanha, N. Ebrahimi Daryani, M.R. Hadiyan, Z. Hallaji, Z. Hussain Khan, M. Kajbaf Zadeh, M.J Mikaeli, A. Mousavi, S.M.J. Mortazavi, B. Nabaei, P. Pasalar , P. Pasbakhsh, M. Rasooli Negad, A. Shaabani, M. Sotoodeh, A.R. Talaeipoor, M. Vahid Dasjerdi, M.R. Zafarghandi International Board: F. Assadi (Chicago), J. Parvizi (Philadelphia), A. Gangi (Strasbourg), M.R. Keshtgar (London), Sh. Masood (Florida), P. Hanjani (Pennsylvania) Editors: N. Behtash, S.B. Hashemi, V. Nikoui, M.A. Noyan Ashraf Office staff: M. Asgari, H. Chaychi, A. Kamizani, R. Ramezani, S. Sadigh Publisher: Tehran University of Medical Sciences Office: Tehran University Medical Journal, Medical School, 202 Amouzesh building, Poursina Ave., Ghods St., Keshavarz Blvd., Tehran, Iran, P.o. Box: 14155-6447, Tel: +98(21)88962510, Fax: +98(21)88962510, Online submission: http://journals.tums.ac.ir/login, and http://tumj.tums.ac.ir, Email: medjournal@tums.ac.ir
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