AMPK信号通路调控的自噬在七氟烷后处理保护大鼠心肌缺血再灌注损伤中的机制研究  

Role of AMPK Signal Transduction Pathway in Protection Mechanism of Sevoflurane Postconditioning Protecting Rat Hearts against Myocardial Ischemia Reperfusion Injury in vivo

作　　者：覃琴[1] 王琛[1] 乔世刚[1] 周迅[1] 

机构地区：[1]苏州大学附属第二医院麻醉科,苏州215004

出　　处：《生物医学工程研究》2016年第1期36-40,45,共6页Journal Of Biomedical Engineering Research

基　　金：江苏省自然科学基金资助项目(BK20141187);苏州市科技计划项目(SYS201473);苏州大学附属第二医院博士;留学归国人员预研项目(SDFEYBS1401)

摘　　要：研究七氟烷后处理对在体大鼠心肌缺血再灌注(I/R)损伤的保护作用,探讨腺苷酸活化蛋白激酶(AMPK)介导的自噬流在七氟烷后处理心肌保护中的作用。成年雄性SD大鼠50只,建立急性大鼠在体心肌I/R损伤模型。随机分为5组:假手术组(Sham组)、缺血再灌注组(I/R组)、七氟烷后处理组(SP组)、Compound c溶剂二甲基亚砜组(DMSO组)、AMPK抑制剂Compound c组(Com c组)。除Sham组,其余各组缺血30 min,再灌注4 h末。再灌注4 h末,提取心脏,采用氯化三苯基四氮唑染色法(TTC法)测定心肌梗死范围。采用免疫印迹法(Western blot技术)检测p-AMPK/t-AMPK、LC3Ⅱ/Ⅰ及P62蛋白表达水平。与I/R组比较,SP组心肌梗死范围减小,p-AMPK/t-AMPK蛋白表达上调而LC3Ⅱ/Ⅰ、P62蛋白表达下调(P<0.05);与SP组比较,Com c组心肌梗死范围增加,p-AMPK/t-AMPK蛋白表达下调而LC3Ⅱ/Ⅰ、P62蛋白表达上调(P<0.05)。DMSO组相比于SP组差别无统计学意义(P>0.05)。七氟烷后处理减轻了在体大鼠心肌I/R损伤,其机制可能是通过激活AMPK信号通路,减少再灌注期间自噬体的蓄积,保护自噬流进而发挥保护作用。To investigate if sevoflurane postconditioning protecting rat hearts against ischemia-reperfusion injury in vivo by restoring impaired autophagosome clearance and the role of AMP-activated protein kinase（ AMPK） signal transduction pathway in it. Fifty adult male Sprague-Dawley rats,weighing 270 ~ 320 g,were randomly divided into 5 groups（ n = 10 each）： Sham operation group（Sham group）,ischemia-reperfusion（I/R group）,sevoflurane postonditioning group（SP group）,sevoflurane postonditioning ＋ selective AMPK inhibitor compound C group（ Com c group） and compound C vehicle dimethyl sulfoxide（ DMSO） group（ DMSO group）.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch（ LAD） of coronary artery followed by 4 h reperfusion,Myocardial infarct size was stained by triphenyltetrazolium chloride. Expression of p-AMPK / t-AMPK、LC3 Ⅱ / Ⅰand P62 were assessed by western blotting. Compared to I / R group,infarct size decreased and the expression of p-AMPK / t-AMPK was significantly up-regulated but LC3 Ⅱ / Ⅰand P62 protein were significantly down-regulated in SP group（ P 0. 05）; compared to SPgroup,infarct size increased and the expression of p-AMPK / t-AMPK was significantly down-regulated but LC3 Ⅱ / Ⅰand P62 protein were significantly up-regulated in Com c group（ P 0. 05）. Sevoflurane postcondition protects rat hearts against myocardial I / R injury in vivo,which may activatie AMPK signal transduction pathway and restoring impaired autophagosome clearance during myocardial reperfusion process.

关 键 词：腺苷酸活化蛋白激酶 麻醉药 吸入 心肌缺血再灌注损伤 自噬流 

分 类 号：R318[医药卫生—生物医学工程]