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The influence and significance of rapamycin on cardiomyocyte autophagy level of early heart failure rat

Objective: To explore the influences of rapamycin on cardiomyocyte autophagy level of early Heart Failure (HF) rat.

Methods: HF rat model was built by abdominal aorta surgery, and then they were randomly divided into the treatment group and the control group. The treatment group was given 3000 U/kg intraperitoneal injection of rapamycin, 3 times per week, for 4 weeks; the control group given the same amount of saline solution. Respectively 4 weeks, 8 weeks, 12 weeks after surgery (i.e., dosing 4 weeks), heart colour ultrasound examination was given for rat cardiac function. After 24 h fasting of all rats at the end of 12 weeks, rats were killed, then to observe the myocardial tissue cell morphology, cell apoptosis and Apoptosis Index (AI); Using Western blot method to detect myocardial Beclin 1, Cathepsin D protein expression.

Results: Echocardiography showed ventricular hypertrophyat 4 weeks , HF at 8 weeks in the model group; rapamycin intervention in the control group after 4 weeks, Left Ventricular Ejection Fraction (LVEF) increased significantly (P<0.05), interventricular septal thickness at end-systole (IVSs), left ventricular posterior wall thickness at end-systole (LVPWs), Interventricular Septum thickness at enddiastole (IVSd), Left Ventricular Posterior Wall Thickness at end-Diastole (LVPWd) significantly decreased after treatment (P<0.05). Compared with the sham group, mTOR expression decreased significantly, cTnT and pmTOR expression increased obviously in the control group (P<0.05); compared with the control group, mTOR expression increased significantly, cTnT and pmTOR expression decreased obviously in the treatment group (P<0.05). AI of the treatment group was significantly lower than Control (25.55% ± 2.56% vs. 34.66% ± 1.46%, P<0.01); compared with the control group (0.234 ± 0.001 and 0.001 ± 0.001), Beclin 1 and Cathepsin D OD value of the control group (0.867 ± 0.005 and 0.867 ± 0.003) increased significantly, the treatment group (0.423 ± 0.002 and 0.002 ± 0.001) was lower than the control group (P<0.01).

Conclusion: Rapamycin can effectively improve cardiac function in heart failure rats, inhibit cardiomyocyte autophagy.

Author(s): Zhang Shuli, Jianhui Zang, Wang Moru