[Rosuvastatin protects acute myocardial infarction rats through autophagy regulation via AMPK signaling]

Abstract

Objective: To investigate the effects of rosuvastatin (RSV)on autophagy and apoptosis of myocardial cells in rats with acute myocardial infarction. Methods: SD rats were divided into control (Sham group), acute myocardial infarction model rats (AMI group), AMI rats treated by RSV with the dose of 5 mg·kg(-1)·d(-1) (RSV group), AMI rats treated by RSV and AMPK inhibitor Compound C at the same time (RSV+ CC group)(n=8) based on simple random sampling methods.Rat myocardial cell line H9c2 was divided into control group, Hypoxia group, Hypoxia+ RSV group, Hypoxia+ RSV+ Compound C group, Hypoxia+ AICAR (AMPK activator)group.After 6 weeks, the rats were examined by hemodynamics, and pathological observation of myocardial tissue by HE staining was also carried out.RT-PCR/Western blot were used to detect the expression of Beclin1, p62, BAX and Bcl-2 mRNA or protein of different groups in vivo and in vitro.Western blot was used to detect the expression of mTOR and AMPK protein and phosphorylation in cardiac tissue of each group. Results: In this study, the rat model of acute myocardial infarction was successfully prepared.Compared with the AMI group, the myocardium inflammation in the RSV group was alleviated, the LVMI decreased significantly, LVSP increased significantly, LVEDP decreased significantly, HR decreased significantly, the absolute value of dP/dTmax and -dP/dTmax increased significantly.The levels of Beclin1 and Bcl-2 mRNA were significantly up-regulated from 0.43 to 2.01 and 0.30 to 0.72, the expression of p62 and BAX mRNA decreased in half, the phosphorylation level of AMPK was significantly up-regulated, and the level of mTOR phosphorylation significantly reduced(P<0.05). These changes were antagonized by AMPK inhibitors in RSV+ CC group.In vitro experiments showed that, after RSV intervening, the levels of Beclin1 and Bcl-2 mRNA and protein in the myocardial cells of Hypoxia group significantly increased in triple, while the expressions of p62 and BAX mRNA and protein significantly decreased above a half.The above changes were consistent with those of the AMPK activator group and were antagonized by Compound C. Conclusion: RSV can effectively promote autophagy and decrease apoptosis in rat heart after myocardial infarction through AMPK/mTOR pathway.

Keywords: AMPK; Autophagy; Myocardial infarction; Rosuvastatin.