Astragaloside protects cardiomyocytes from rats with heart failure by regulating Caspase-3

Abstract

The ultimate manifestation of several heart diseases is heart failure, which is closely related to cardiac insufficiency, ventricular remodeling, and cytokine system activation. This study mainly assessed whether astragaloside regulates Caspase-3 by controlling Bcl-2/Bax pathway to protect cardiomyocytes in heart failure. Five groups were set up as model group, Bcl-2 inhibitor (ABT-199) group, Bax inhibitor (BIP-V5) group, low-dose and high-dose astragaloside group. Hematoxylin-eosin(HE) staining, CCK-8, Transwell method and flow cytometry measured histopathology of mouse myocardial tissue, proliferation, migration and apoptosis of cardiomyocytes respectively, and pathway-related genes, proteins and Caspase-3 levels were also measure. According to HE staining, the banding and cell swelling of three groups treated with astragaloside were significantly improved compared with model group, and the higher the concentration was, the more was significant improvement. Astragaloside inhibited Caspase-3 and Bax expressions and up-regulated Bcl-2 expression (all P < 0.05). The apoptosis of cardiomyocytes was related to Bcl-2 in the heart failure process, and apoptosis was controlled after using Bcl-2 mimics, but inhibition of Bax also showed a consistent trend. When Bcl-2/Bax ratio was increased, Caspase-3 was down-regulated. Astragaloside can promote increased Bcl-2/Bax ratio, mediate decreased Caspase-3 level in the cardiomyocytes, thereby inhibiting apoptosis. By increasing the concentration of astragaloside, the expression of Bcl-2/Bax can be up-regulated, which can further inhibit Caspase-3 expression, thereby reducing the damage of cardiomyocytes in heart failure tissue, and also inhibiting cell apoptosis.