Protective effect of PGSF on myocardial ischemia injury induced by ISO in neonatal rats and its possible mechanism / 中国医师杂志

ABSTRACT

Objective:To study the protective effect of polygalasaponin F (PGSF) on isoproterenol (ISO)-induced myocardial ischemia (MI) injury in neonatal rats and its possible mechanism.Methods:Fifty newborn Sprague Dawley (SD) rats were randomly divided into control group, model group, low, medium and high dose PGSF groups (5, 10, 50 mg/kg), with 10 rats in each group. The rats in the control group were treated with normal saline; Myocardial ischemia (MI) model was established in model group by subcutaneous injection of isoproterenol (ISO, 85 mg/kg, once a day); The MI model was established in rats of low, medium and high dose PGSF group after intraperitoneal injection of 5, 10 and 50 mg/kg PGSF for 7 days. The cardiac function of rats in each group was evaluated by echocardiography; pathological changes of myocardial tissue of rats in each group were observed by hematoxylin and eosin (HE) staining; The serum activities of troponin I (cTnI), creatine kinase isoenzyme (CK-MB), myoglobin (Mb) and lactate dehydrogenase (LDH) of rats in each group were detected by enzyme linked immunosorbent assay (ELISA); the content of malondialdehyde (MDA) and active oxygen species (ROS) in myocardial tissue were detected ; the expression of nuclear proliferation antigen (Ki67) and caspase-3 protein in myocardial tissue was detected by immunohistochemical staining; The expression of protein kinase B (AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein in myocardium was detected by Western blot.Results:In the model group, the myocardial structure was disordered, the cells were congested and swollen, and there were a lot of inflammatory cells infiltrating and large necrotic foci. The left ventricular wall thickness (LVWT), left ventricular ejection fraction (LVEF), fractional shortening (FS), heart rate (HR) and expression of Ki67 positive protein in the model group were lower than those in the control group (all P<0.05), while the left ventricular end systolic volume (LVESV), activities of cTnI, CK-MB, Mb, LDH in serum, content of ROS and MDA in myocardial tissue and caspase-3 positive protein in the model group were higher than those in the control group (all P<0.05). Compared with the model group, the degree of myocardial pathological changes in neonatal rats of the low, medium and high dose PGSF groups gradually decreased. Compared with model group, the LVWT, LVEF, FS, HR and expression of Ki67 positive protein increased in low, medium and high dose PGSF groups (all P<0.05), while the LVESV, activities of cTnI, CK-MB, Mb and LDH in serum, content of ROS and MDA in myocardial tissue and the expression of caspase-3 positive protein decreased (all P<0.05); Western blot results showed that the relative expression of phosphorylated(p)-AKT/AKT, p-Nrf2/Nrf2 protein in myocardium of model group was lower than that of control group (all P<0.05); The relative expression of p-AKT/AKT, p-Nrf2/Nrf2 protein in myocardium of low, medium and high dose PGSF groups were higher than that in the model group (all P<0.05). Conclusions:PGSF has protective effect on MI injury in neonatal rats, and its mechanism may be related to anti-apoptosis and anti-oxidative stress.