粉防己碱预处理减轻大鼠肝脏缺血再灌注损伤的机制研究.docx

粉防己碱预处理减轻大鼠肝脏缺血再灌注损伤的机制研究【摘要】目的研究粉防己碱(tetrandrine,TET)预处理对大鼠肝缺血再灌注损伤的预防作用及其机制。方法大鼠肝脏左中叶缺血50min，再灌注24h后处死(I/R组)，TET+I/R组缺血前30min腹腔注射TET(50mg/kg)，余同I/R组。大鼠处死前采血检测丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),乳酸脱氢酶(LDH),取缺血肝组织进行超氧化物歧化酶(SOD),一氧化氮(NO)，丙二醛(MDA)，湿重干重(W/D)比检测和组织学检查。结果I/R组血清ALT,AST和LDH升高，组织MDA水平,W/D比值也明显升高，SOD活性和NO含量下降。在TET+I/R组，血清ALT,AST,LDH，以及组织W/D比值较I/R组降低，SOD活性和NO含量升高。此外，TET+I/R组大鼠血清ALT,AST,组织MDA和W/D比值较假手术组升高，SOD活性和NO含量降低.组织学检查显示TET+I/R组肝损害减轻。结论TET能减轻但不能防止肝I/R损伤的发生，减少脂质过氧化物产生是TET抗I/R损伤的原因之一。【关键词】粉防己碱；缺血再灌注；大鼠【Abstract】ObjectiveTheeffectoftetrandrine(TET)pretreatmentofWistarratssubjectedtowarmhepaticischemia/reperfusion(I/R)wasAfter50minutesofischemiaintheleftandmedianlobesoftheliverand24hoursofreperfusion(I/Rgroup),theratswereTET+I/RgroupratswerepretreatedwithTET(50mg/kgbodyweightIP)30minutespriortotheonsetofsamplesweretakenformeasurementofalanineaminotransferase(ALT),aspartateaminotransferase(AST),andlactatedehydrogenase(LDH).Tissuewastakenfromtheischemiclobesformeasurementofsuperoxidedismutase(SOD),malonyldialdehyde(MDA),andmyeloperoxidase(MPO);determinationofthewet/dryweight(W/D)ratio;andhistologicTheresultsshowedthatALT,AST,andLDHlevelsinserumwereincreasedintheI/Rgroup;tissueMDAgeneration,MPOactivity,andtheW/Dratiowerealsoincreased,accompaniedbydecreasedSODserumALT,AST,andLDHlevels,aswellasthetissueMPOlevelandW/Dratio,werelowerintheTET+I/RgroupthanintheI/Rgroup;andtheSODlevelwashigherintheTET+IRgroupthanintheI/R,theserumALTandAST,tissueMDA,andW/DratiointheTET+I/Rgroupwerehigher,andtheSODwaslowerthanintheshamhistologicexaminationshowedprotectionagainstliverdamageintheTET+I/RTheresultsdemonstratedthatpretreatmentwithTETcouldsomewhatprotecttheliveragainstI/RinjurybutdoesnotpreventsimultaneousdecreaseofbothlipidperoxidegenerationandpolymorphonuclearneutrophilinfiltrationintheischemiclivermayexplaintheacquisitionoftolerancefollowingadministrationofTET.【Keywords】Tetrandrine;Ischemiareperfusion;Rat粉防己碱(tetrandrine,TET)是千金藤属防己科植物粉防己的主要活性成分，属双苄基异喹啉类。近年来国内外对TET药理作用机制进行了较为广