远距后处理对心肌缺血/复灌损伤中线粒体渗透性转换及细胞凋亡的影响  

Effect of remote ischemic postconditioning on mitochondrial permeability transition and apoptosis in myocardial ischemia/reperfusion injury

作　　者：于影[1] 李正红[1] 胡杰[1] 叶红伟[1] 关宿东[1] 高琴[1] 

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233030

出　　处：《中国药理学通报》2011年第4期548-552,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81000074);安徽省高校优秀青年人才基金资助项目(No2009SQRZ128);蚌埠医学院科研课题(NoBY1007)

摘　　要：目的研究远距后处理对大鼠心肌缺血/复灌损伤的保护作用,并探讨其对线粒体渗透性转换孔及细胞凋亡的影响。方法 60只♂Sprague-Dawley大鼠随机分成5组(n=12):假手术组(Sham)、缺血/复灌组(I/R)、远距后处理组(Rpost C)、远距后处理+Atr组(Rpost C+Atr)、缺血/复灌+Atr组(I/R+Atr)。所有组大鼠开胸后冠状动脉左前降支(LAD)下穿线。除Sham组之外,其余各组均LAD缺血45min复灌180 min。Rpost C组:LAD缺血15 min后,同时给予右侧股动脉结扎模拟缺血5 min,松开结扎线复灌5 min,重复循环3次;Rpost C+Atr组:同Rpost C组,并于复灌前30 s静脉注射线粒体渗透性转换孔开放剂苍术苷(Atr,5 mg.kg-1);I/R+Atr组:同I/R组,并于复灌前30 s静脉注射Atr。连续监测动脉血压和心率变化。实验结束后测定血浆乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;检测心肌梗死面积;心肌组织细胞caspase-3的活性;RT-PCR测定左心室前壁心尖组织Bax、Bcl-2 mRNA表达。结果与I/R组相比,Rpost C组LDH、CK、MDA含量均降低,SOD活性增加,心肌梗死面积减小,caspase-3活性减弱,Bcl-2/Bax mRNA比值增高。线粒体渗透性转换孔开放剂Atr减弱Rpost C的作用。结论远距后处理对心肌缺血/复灌损伤有明显的保护作用,其机制可能与抑制线粒体渗透性转换孔的开放和抑制细胞凋亡有关。Aim To observe the cardioprotection of remote ischemic postconditioning（Rpost C） and investigate the effect of mitochondrial permeability transition pore（MPTP） and apoptosis in Rpost C＇s protection.Methods Anesthetized male Sprague-Dawley rats were randomly divided into five groups（n=12）：sham group,ischemia/reperfusion（I/R） group,remote ischemic postconditioning（Rpost C） group,Rpost C＋Atr group and I/R＋Atr group.The left anterior descending coronary arteries（LAD） of all rats were encircled with a suture to make a snare after their chests being opened.Except for sham group,all hearts were exposed to 45 min ischemia followed by l80 min reperfusion.Rpost C group： three cycles of 5 min ischemia by clamping femoral artery and 5 min reperfusion by declamping before myocardial reperfusion.Rpost C＋Atr group： atractyloside（Atr,5 mg·kg-1,a MPTP opener） was intravenously administered 30 s before myocardial reperfusion in Rpost C group.I/R＋Atr group： Atr was administered for 30 s via intravenous method before myocardial reperfusion in I/R group.Throughout the experiment,mean arterial pressure（MAP） and heart rate（HR） were measured.At the end of reperfusion,arterial blood sample was obtained to measure plasma contents of lactate dehydrogenase（LDH）,creatine kinase（CK）,malondialdehyde（MDA） and the activities of superoxide dismutase（SOD）.Infarct size was evaluated using triphenyltetrazolium chloride（TTC） staining method.The activities of caspase-3 of left anterior myocardium were measured by spectrophotometer and the expressions of Bcl-2 and Bax mRNA levels were detected by RT-PCR analysis.Results Compared with I/R,the contents of CK,LDH and MDA were decreased,the activities of SOD were increased,the infarction size and the activities of caspase-3 were reduced,and the ratio of Bcl-2/Bax mRNA were decreased in Rpost C group.However,the protective effect of Rpost C was reduced by Atr.Conclusions Remote ischemic postconditioning produces the protective effect

关 键 词：远距后处理 心肌保护 缺血/复灌损伤 凋亡 线粒体渗透性转换孔 苍术苷 

分 类 号：R-332[医药卫生] R322.11