摘要 : Objective: The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms. Methods: Mouse MI was established by the ligation of the ... 展开 Objective: The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms. Methods: Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy. Results: Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expres-sions of TGF-beta 1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H2O2-treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H2O2. Conclusions: Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-beta/Smad signaling pathway. 收起