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

ZHANG Bin, MA Qian, MA Fu-zhen, WANG Jing, LIU Xu-dong, HE Ru-hua

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.  Methods  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.   Restults  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.  Conclusion  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.

 

Keywords: Astragaloside Ⅳ, Hypoxia/reoxygenation injury, PI3K/AKT pathway, Autophagy

 

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