Dapagliflozin improved ventricular remodeling and depressive behavior in post-infarction depressed rats through SIRT1/NLRP3 signal

Abstract

Abstract Myocardial infarction(MI)is often associated with depression. Studies have shown that Dapaglifozin(DAPA) has a dual protective effect on Cardiac function and depression. This study aimed to determine the protective effect of DAPA in post-myocardial infarction depression༈Post-MI depression༉rats. Male Sprague-Dawley rats were divided into 5 groups: Control, Myocardial infarction, Depression, Post-MI depression, and Post-MI depression + DAPA groups. The effects of DAPA were detected by echocardiography, hemodynamic tests, behavioral tests, Sirius red staining, H&E staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, fluorimetry, and Flow cytometry. We also cultured rat h9c2 cardiomyocytes in vitro to verify the mechanism of action. We found that taking DAPA significantly improved cardiac function and depressive behavior in rats after myocardial infarction. In addition, DAPA could reduce pyroptosis by upregulating of SIRT1 and downregulating of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In vitro experiments, we found that a specific SIRT1 inhibitor can significantly reverse pyroptosis in infarcted myocardial cells. This further indicated that the improvement of DAPA in rats with post-myocardial infarction depression is dependent on the SIRT1/NLRP3 pathway.