Effect of Acanthopanax Giraldii Harms Var Hispidus Hoo polysaccharides on cardiomyocyte apoptosis and expression of related genes in rats with heart failure and its mechanism

Objective To investigate the effect of Acanthopanax Giraldii Harms Var Hispidus Hoo polysaccharides (AGP) on cardiomyocyte apoptosis and PI3K/AKT signaling pathway in rats with heart failure. Methods : A total of 120 specific-pathogen-free SD rats aged 2~3 months old (female/male ratio=1) were randomly divided into the sham operation group, heart failure model group and AGP low-, medium-and high-dose groups (n=20 each) . The AGP low-, medium-, and high-dose groups were injected subcutaneously with AGP (10, 20 and 30 mg·kg-1·d-1) , and the sham-operated group and the model group were injected subcutaneously with the same amount of normal saline. At 4d after pre-administration, the heart failure rat model was established by ligation of the left anterior descending coronary artery. At 42 d after modeling, the left ventricular short axis shortening (FS) and left ventricular ejection fraction (EF) were determined by ultrasound. The activity of superoxide dismutase (SOD) and level of malondialdehyde (MDA) were examined by pyrogallol method and thiobarbituric acid method, respectively. The apoptosis rate of cardiomyocytes was determined by TUNEL kit. The protein expression levels of Bcl-2, Bax, PI3K and p-ATK were measured by Western blotting. Results Compared with the sham operation group, the EF and FS values in the model group were significantly lower[ (31.88±2.56) % vs. (99.71±0.42) %, (18.02±1.52) % vs. (91.12±3.44) %, both P<0.05) ], the SOD activity was significantly reduced[ (90.21±6.12) nU/ml vs. (124.93±8.87) nU/ml, P<0.05) ], the MDA level significantly increased[ (6.47±0.68) nmol/ml vs. (3.68±0.39) nmol/ml, P<0.05) ], the apoptosis rate of cardiomyocytes increased significantly[ (22.38±1.42) % vs. (5.02±0.51) %, P<0.05) ], the protein expression levels of Bcl-2, PI3K and p-ATK significantly decreased (0.087±0.010 vs. 0.762±0.059, 0.052±0.005 vs. 0.859±0.072, 0.021±0.005 vs. 0.151±0.016, all P<0.05) , and the protein expression level of Bax significantly increased (0.087±0.010 vs. 0.762±0.059, P<0.05) . Compared with the model group, the EF and FS values, the SOD activity in the low-, medium-and high-dose AGP groups significantly increased (all P<0.05) , the MDA level and the apoptosis rate of cardiomyocytes significantly decreased (all P<0.05) , the protein expression levels of Bcl-2, PI3K and p-ATK significantly increased (all P<0.05) , and the protein expression level of Bax significantly decreased in a concentration-dependent manner (P<0.05) . Conclusion AGP may reduce cardiomyocyte apoptosis in rats with heart failure. The mechanism may be related to the inhibition of oxidative stress and activation of PI3K/AKT signaling pathway. Key words: Heart failure rats; Myocardial cells; Acanthopanax giraldii Harms Var Hispidus Hoo polysaccharides; Apoptosis