雷帕霉素在冠状动脉左前降支结扎诱导的大鼠心肌梗死中的作用研究  

Role of rapamycin in rat model of myocardial infarction induced by left anterior descending coronary artery

作　　者：陈溪[1] 曾泗宇[2] 高利臣[1] 史群志[1] 文丹丹[1] 刘芳群[1] 

机构地区：[1]长沙市中心医院药学部,长沙410004 [2]广东省第二人民医院药物临床试验基地,广州510317

出　　处：《中南药学》2016年第5期488-492,共5页Central South Pharmacy

基　　金：长沙市中心医院院内科研重点项目(No.201402);广东省自然科学基金博士启动项目(No.2015A030310076)

摘　　要：目的探索雷帕霉素在冠状动脉左前降支结扎(LAD)诱导的心肌梗死模型中对于左室功能失代偿以及心肌能量代谢紊乱的改善作用。方法结扎大鼠冠状动脉左前降支构建心肌梗死模型后腹腔注射给予雷帕霉素;采用Western blot监测自噬相关蛋白LC3、p62/SQSTM1变化、冰冻切片-免疫荧光观测心肌自噬小体数量,并以此判定肥大心肌细胞中自噬潮的变化;通过超声心动图检测评价雷帕霉素观察激活自噬在LAD诱导的心肌梗死中对于左室功能的影响;采用透射电镜、荧光定量仪分析心肌组织线粒体结构及心肌组织ATP供应的情况。结果 LAD诱导的大鼠心肌梗死模型中,LC3-Ⅱ表达下降、p62/SQSTM1表达升高;与LAD组比较,雷帕霉素组可明显改善LAD诱导的左室射血分数下降、维持心肌线粒体结构和ATP能量供应。结论自噬潮在LAD诱导的心肌梗死受到阻断,雷帕霉素能够改善LAD诱发的左室功能障碍和心肌线粒体能量代谢紊乱。Objective To investigate the role of rapamycin in ameliorating left ventricular dysfunction and car- diac energy metabolism disorders induced by left anterior descending coronary artery （LAD）. Methods In this study, rapamycin was administrated intraperitoneally for one week after the rat model of myocardial infarction induced by LAD was established. Western blot and immunofluorescence analysis were performed to evaluate the autophagic flux in the infarcted hearts. Additionally, we performed ECG and TEM analysis to determine the left ventricular and mitochondrial function, respectively. Results The protein expression of LC3- II was downregulated, whereas the expression of p62/SQSTM1 was up-regulated in the infarcted hearts. Compared with the LAD group, rapamycin was demonstrated to attenuate left ventricular dysfunction and maintain the mitochon- drial structure and ATP production in hearts induced by LAD. Conclusion Autophagic flux was blocked in the infarcted hearts, and rapamycin was able to attenuate LAD-induced cardiac dysfunction, maintained the struc- ture integrity and functional performance of mitochondria.

关 键 词：雷帕霉素 心肌梗死 自噬 能量代谢 

分 类 号：R285.5[医药卫生—中药学]