Grape seed proanthocyanidin extract improves myocardial function in rats with myocardial infarction by inhibiting PARP-1 activity

Abstract

Objective To observe the improvement effect of grape seed proanthocyanidin extract (GSPE) on myocardial function in rats with myocardial infarction and to explore its mechanism. Methods Myocardial infarction model rats were randomly divided into five groups: model group, GSPE low, middle and high group, poly ADP-ribose polymerase-1 (PARP-1) inhibitor BSI-201 group, with 15 rats in each group, and another 15 rats were as the sham operation control group. Rats in GSPE low, medium and high dose groups were administrated with 100 mg/ml GSPE, 200 mg/ml GSPE and 400 mg/ml GSPE respectively; BSI-201 group was given 120 μmol/L BSI-201 of gavage, and the control group and model group were treated with equal volume of normal saline of gavage, 1 times a day for 4 weeks. Doppler echocardiography was used to evaluate cardiac function in rats; myocardial infarction volume was detected by three-phenyl tetrazolium chloride (TTC) staining; hematoxylin and eosin (HE) staining was used to detect histopathological changes of myocardial tissue; terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of myocardial cells; Western blot was used to analyze the expressions of Bax, cleaved-caspase3, Bcl-2 and PAR in myocardial tissue. Results Compared with the control group, the heart rate, left ventricular end diastolic pressure, myocardial infarction area and cell apoptosis rate were significantly increased in the model group, and the mean arterial pressure and left ventricular systolic pressure were decreased significantly (P<0.05); Myocardial cells were broken and necrotic, irregular fibers arranged in the myocardium, and a large number of inflammatory cells were infiltrated; the protein expressions of Bax, cleaved-caspase3 and PAR in myocardial tissues were increased significantly (P<0.05), and the protein expression of Bcl-2 was significantly decreased (P<0.05). Compared with the model group, the heart rate, the left ventricular end diastolic pressure, myocardial infarction area and cell apoptosis rate in the GSPE low, middle and high dose groups and the BSI-201 group were significantly decreased, and the mean arterial pressure and the left ventricular systolic pressure were increased significantly (P<0.05); the degree of histopathological damage was alleviated; the expressions protein of Bax, cleaved-caspase3 and PAR in myocardial tissues were decreased significantly (P<0.05), and the protein expression of Bcl-2 was increased significantly (P<0.05). Conclusions Grape seed proanthocyanidin extract may inhibit cardiomyocyte apoptosis and improve myocardial function of rats with myocardial infarction by inhibiting PARP-1 activation. Key words: Proanthocyanidins/PD; Poly(ADP-ribose) polymerases/DE; Myocardial infarction/DT; Apoptosis; Rats