吗啡后处理对大鼠离体缺血再灌注心肌自噬的影响  

Effects of morphine postconditioning on autophagy induced by ischemia-reperfusion in isolated rat hearts

作　　者：赵其宏[1,2] 张颖 沙磊 Zhao Qihong;Zhang Ying;Sha Lei(Dept of Anesthesiology,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233004;Dept of Anesthesiology,The Third Affiliated Hospital of Southern Medical University,Guangzhou 510630)

机构地区：[1]蚌埠医学院第一附属医院麻醉科,蚌埠233004 [2]南方医科大学第三附属医院麻醉科,广州510630

出　　处：《安徽医科大学学报》2018年第12期1871-1874,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高等学校自然科学研究项目(编号:KJ2015B032by)

摘　　要：目的研究吗啡后处理(PC)对离体大鼠缺血再灌注心肌自噬的影响及其可能机制。方法成年雄性SD大鼠48只,随机分为3组:空白对照组(C组),缺血再灌注组(I/R组),吗啡PC组(M组),每组16只。采用Langendorff心脏灌流装置构建大鼠离体心肌缺血再灌注模型。C组持续灌注110 min,另两组平衡灌注20 min后实行30 min缺血、60 min再灌注; M组于再灌注开始前即刻给予1μmol/L吗啡灌流15 s、洗脱15 s,共重复4次。再灌注末,检测冠脉流出液肌酸激酶(CK)活性,分析心肌梗死面积,观察心肌病理学变化,Western blot测定心肌组织微管相关蛋白1轻链3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ)以及哺乳动物雷帕霉素靶蛋白(m TOR)、磷酸化m TOR(p-mTOR)的表达。结果与I/R组比较,M组CK活性显著降低(P <0. 01),心肌梗死面积显著减小(P<0. 01),心肌病理学改变较轻,LC3-Ⅱ/Ⅰ比值明显降低(P<0. 01)、p-mTOR表达增高(P <0. 01)。结论吗啡PC通过激活m TOR抑制缺血再灌注诱导的心肌自噬,并进一步减轻心肌缺血再灌注损伤。Objective To investigate effects of morphine postconditioning(PC)on autophagy induced by ischemia-reperfusion in isolated rat hearts and its possible mechanism.Methods 48 male adult SD rats were randomly divided into three groups:blank control group(C group),ischemia-reperfusion group(I/R group),morphine PC group(M group),16 rats in each group.A Langendorff perfusion device was used to simulate myocardial ischemia-reperfusion model in isolated rat hearts.In group C,continuous perfusion was performed for 110 min,and the other two groups were subjected to 30 min of ischemia followed by 60 min of reperfusion after 20 min of balanced perfusion.M group was given 1μmol/L morphine perfusion for 15 s and elution for 15 s immediately,which was repeated 4 times just before reperfusion.At the end of reperfusion,the activity of creatine kinase(CK)in the coronary effluent was measured,and myocardial infarct size was analyzed,and pathological changes of the myocardium was observed,and the expression of microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),mammalian rapamycin target protein(mTOR)and phosphorylated mTOR(p-mTOR)was determined by Western blot in myocardial tissue.Results Compared with I/R group,CK activity was significantly decreased(P<0.01),and myocardial infarct size was significantly reduced(P<0.01),and myocardial pathological changes were lighter,and LC3-Ⅱ/Ⅰratio was significantly decreased(P<0.01),and the expression of p-mTOR was increased(P<0.01)in M group.Conclusion Morphine PC alleviates myocardial ischemia-reperfusion injury by ameliorating the enhancement of myocardial autophagy induced by ischemia-reperfusion via activating mTOR.

关 键 词：吗啡 再灌注损伤 后处理 自噬 

分 类 号：R961[医药卫生—药理学]