Compound Danshen Tablets ameliorate myocardial ischemia/reperfusion injury-induced ventricular remodeling by regulating autophagy via AMPK/mTOR signaling pathway
Qiaoyu Li, Yun Luo, Haibiao Guo, Wenxiu Liu, Hui Yu, Chuyuan Li, Rongchang Chen, Xiaobo Sun
Abstract
Objective: Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. Methods: The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. Results: ), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. Conclusion: CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.