雷帕霉素对早期心力衰竭大鼠心肌细胞自噬功能的影响及意义  

Effect and significance of rapamycin on cardiomyocyte autophagy function in early heart failure rat

作　　者：杨韶华[1] 李雅倩[2] 周佾龙[3] 张斌[4] 

机构地区：[1]河南省三门峡市中心医院ICU,三门峡472000 [2]南昌大学第一临床医学院,南昌330000 [3]河南科技大学附属三门峡市中心医院急诊科,三门峡472000 [4]河南科技大学附属三门峡市中心医院ICU,三门峡472000

出　　处：《重庆医科大学学报》2017年第9期1156-1160,共5页Journal of Chongqing Medical University

摘　　要：目的:探讨雷帕霉素对早期心力衰竭大鼠心肌细胞自噬功能的影响。方法:采用腹主动脉缩窄术方法建立心力衰竭大鼠模型并分为对照组(n=8)和治疗组(n=6)。治疗组大鼠每周腹腔注射雷帕霉素(3 000 U/kg)3次,总共4周;以生理盐水腹腔注射作为对照。于术后4、8、12周的不同时间点进行心脏彩超。全部大鼠在第12周末经过24 h禁食后处死,观察心肌组织细胞形态、心肌细胞凋亡及计算凋亡指数(AI);应用蛋白免疫印迹方法检测Cathepsin D和Beclin-1的蛋白表达水平。结果:超声心动图显示建模后4周时出现心室肥厚,8周时出现心力衰竭。治疗组AI较对照组明显降低[(25.55±2.56)%vs.(34.66±1.46)%,P<0.05)];与假手术组相比较;对照组(0.867±0.005,0.821±0.003)的Beclin-1和Cathepsin D的OD值明显升高,治疗组(0.423±0.002,0.655±0.001)较对照组降低(P<0.01)。假手术组、治疗组、对照组的心肌细胞自噬率分别为(8.14±1.27)%、(26.73±2.48)%、(34.57±4.06)%(F=1.998,P=0.046)。结论:雷帕霉素能降低心肌细胞自噬发生,改善心力衰竭大鼠的心脏功能。Objective：To explore the effect and significance of rapamycin on cardiomyocyte autophagy function in early heart failure rat. Methods：The rats were divided into control group（n=8）and treatment group（n=6）. The heart failure model was established by abdominal aortic constriction. Rats in the treatment group were intraperitoneally injected with rapamycin（3 000 U/kg） 3 times per week for 4 weeks;saline was injected intraperitoneally as control. At 4 weeks,8 weeks,12 weeks after operation,the patients were examined at different time points. All rats were sacrificed at the end of the 12 th week after 24 hours of fasting. Myocardial cell morphology,myocardial cell apoptosis and apoptosis index（AI）were observed. Protein expression of Cathepsin D and Beclin-1 was detected by Western blot. Results：Echocardiography showed ventricular hypertrophy at 4 weeks after modeling and heart failure at 8weeks. The AI was lower in treatment group than in control group[（25.55±2.56）% vs.（34.66±1.46）% ,P〈0.05]. The levels of Beclin-1 and Cathepsin were significantly higher in the control group（0.867±0.005 and 0.821±0.003）than in sham operated group,and the levels of Beclin-1 and Cathepsin were lower in treatment group（0.423±0.002 and 0.655±0.001）than in control group（P〈0.01）.The cardiomyocyte autophagy rate in sham-operated group,treatment group and control group were（8.14±1.27）% ,（26.73±2.48）% ,（34.57±4.06）% （F=1.998,P=0.046）. Conclusion：Rapamycin can effectively inhibit cardiomyocyte autophagy and improve cardiac function in rats with heart failure.

关 键 词：雷帕霉素 心力衰竭 自噬 

分 类 号：R541.6[医药卫生—心血管疾病]