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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 investigate the effect of rapamycin on cardiac myocyte autophagy in early heart failure rats. Methods: A rat model of heart failure was established by abdominal aortic constriction and divided into control group (n = 8) and treatment group (n = 6). Rats in the treatment group were injected with rapamycin (3 000 U / kg) three times per week for a total of 4 weeks; saline as a control was intraperitoneally injected. At 4, 8 and 12 weeks after surgery, echocardiography was performed at different time points. All rats were sacrificed at the end of the twelfth week after 24 h of fasting. The morphological changes of myocardial cells and apoptosis of cardiomyocytes were observed. The protein expression of Cathepsin D and Beclin-1 was detected by Western blotting . Results: Echocardiography showed ventricular hypertrophy 4 weeks after modeling and heart failure 8 weeks later. Compared with the sham-operation group, the AI in the treatment group was significantly lower than that in the control group [(25.55 ± 2.56)% vs (34.66 ± 1.46)%, P <0.05) OD of Cathepsin-1 and Cathepsin D were significantly higher in treatment group (0.423 ± 0.002, 0.655 ± 0.001) than those in control group (P <0.01). The autophagy rate of cardiomyocytes in sham operation group, treatment group and control group were (8.14 ± 1.27)%, (26.73 ± 2.48)% and (34.57 ± 4.06)%, respectively (F = 1.998, P = 0.046). Conclusion: Rapamycin can reduce the cardiomyocyte autophagy and improve heart function in heart failure rats.