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

发布时间：2018-08-18 12:02

【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)%,P0.05)];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(P0.01)。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。
[Abstract]:Aim: to investigate the effect of rapamycin on cardiac myocyte autophagy in rats with early heart failure. Methods: the rat model of heart failure was established by abdominal aortic coarctation and divided into two groups: control group (n = 8) and treatment group (n ~ (6). Rats in the treatment group were intraperitoneally injected rapamycin (3 000 U/kg) three times a week for a total of 4 weeks, and saline intraperitoneal injection was used as the control. Cardiac color Doppler ultrasound was performed at different time points of 4 ~ 8 ~ 12 weeks postoperatively. All the rats were killed after 24 h fasting at the 12th week. The morphology, apoptosis of myocardial cells and the expression of Cathepsin D and Beclin-1 protein were detected by Western blotting method and the apoptotic index (AI);) was calculated. Results: echocardiography showed ventricular hypertrophy at 4 weeks after modeling and heart failure at 8 weeks. The AI of the treatment group was significantly lower than that of the control group [(25.55 卤2.56) vs (34.66 卤1.46) vs the sham-operated group], the OD values of Beclin-1 and Cathepsin D in the control group (0.867 卤0.005 卤0.821 卤0.003) were significantly higher than those in the control group (0.423 卤0.002 卤0.655 卤0.001), and the OD values in the treatment group (0.423 卤0.002 卤0.655 卤0.001) were lower than those in the control group (P0.01). The autophagy rates of cardiac myocytes in sham operation group, treatment group and control group were (8.14 卤1.27), (26.73 卤2.48), (34.57 卤4.06)% (F ~ (1.998) P ~ (0.046), respectively. Conclusion: rapamycin can reduce myocardial autophagy and improve cardiac function in heart failure rats.
【作者单位】：河南省三门峡市中心医院ICU;南昌大学第一临床医学院;河南科技大学附属三门峡市中心医院急诊科;河南科技大学附属三门峡市中心医院ICU;
【分类号】：R541.6

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