Astragaloside Ⅳ's Therapeutic Effect on Myocardial Infarction via Affecting Autophagy and the Mechanism Study

Abstract

The purpose of this study was to investigate the protective effect of astragaloside Ⅳ (AS-Ⅳ) on neonatal rats' hypoxic/reoxygenated (H/R) injured myocardial cells and to explore its underlying mechanism. Cardiac cells were extracted from newborn rats and divided into control, H/R, H/R-low AS-Ⅳ (0.1 μmol/L AS-Ⅳ), H/R-medium AS-Ⅳ (1 μmol/L AS-Ⅳ), H/R-high AS-Ⅳ (10 μmol/L AS-Ⅳ) and H/R-high AS-Ⅳ-AKT (10 μmol/L AS-Ⅳ+5 μmol/L AKT) groups. After 48 h of treatment, the contents of LC3-Ⅱ, p62, AKT, pAKT, rapamycin (mTOR) mammalian targets and uncoordinated 51-like kinase 1 (ULK1) in cardiac myocytes were compared. Immunofluorescence staining was used to detect the expression of P62 in myocardium autophagosome. AS-Ⅳ improved the proliferative activity of cardio AS-Ⅳ improved the proliferative activity of cardiomyocytes in H/R injury in a dose-dependent manner and inhibited the level of cell autophagy. However, when AKT inhibitors were added, the effect of AS-Ⅳ was partially inhibited ( P<0.05). Gene and protein expression showed that AS-Ⅳ had no significant effect on the expression of AKT and mTOR genes ( P>0.05), but could significantly promote the phosphorylation of AKT and mTOR ( P<0.05). Immunofluorescence staining results showed that high concentrations of the AS - Ⅳ can reverse H/R injury induced the expression of autophagy body P62. AS-Ⅳ showed protection effect on H/R injured myocardial cells. The possible mechanism is by reducing the autophagy level via activating the mTOR signal in the PI3K/AKT pathway, thereby preventing H/R damage in neonatal rat cardiomyocytes.