Abstract
OBJECTIVES: To investigate the protective effect of isovitexin (ISO) on the myocardium of diabetic mice and explore its mechanism. METHODS: Eighteen adult male C57 mice were randomly divided into control group, diabetes mellitus (DM) group and DM+ISO group (n=6). Primary cultures of neonatal mouse cardiomyocytes (NMCMs) were exposed to high glucose (33 mmol/L) and treated with ISO alone or in combination with 3-TYP (a SIRT3 inhibitor). HE staining was used to evaluate myocardial injury in the diabetic mice, and the levels of MDA, SOD and GSH-Px in the myocardium were detected with ELISA. The expressions of iNOS, NOX2 and 8-OHdG were detected using immunohistochemistry and fluorescence staining. Western blotting was used to analyze the expression levels of NRF2, NOX2, NQO1, and SIRT3, and ROS levels were determined with flow cytometry. RESULTS: The diabetic mice showed obvious inflammatory cell infiltration in the myocardium, increased myocardial levels of IL-1β, IL-6 and TNF‑α, decreased expression levels of NQO1, NRF2 and SIRT3 proteins, and increased expression levels of NOX2 and AC-SOD2 proteins. ISO treatment of the diabetic mice significantly reduced myocardial inflammatory cell infiltration, lowered the levels of IL-1β, IL-6 and TNF‑α, restored the protein levels of NQO1, NRF2 and SIRT3, and decreased the protein levels of NOX2 and AC-SOD2. CONCLUSIONS: ISO can alleviate diabetic myocardial injury in mice by promoting SIRT3 expression and reducing oxidative stress.