PP.14.20

Abstract

Objective: Metabolic syndrome (MS) was the major risk factors for heart failure, initially manifesting as diastolic dysfunction. In this present study, the effects and the mechanisms of astragaloside IV (AST) were investigated on high fructose/high fat diet (HFFD) induced MS rats. Design and method: The rat MS model was established by feeding HFFD for 24 weeks. Rats were divided into four groups as normal control group, MS group, MS+AST 0.5 (0.5 mg/kg, i.p.) group and MS+AST 2 (2 mg/kg, i.p.) group. The hemodynamic and echocardiographic parameters were used to assess the left ventricular functions. Rat left ventricular tissue and plasma samples were collected for biochemical and molecular analysis. Results: Our HFFD fed rats had hypertriglyceridaemia, high blood glucose, hyperinsulinemia, elevated blood pressure, weight gain, and diastolic dysfunction. AST could improve diastolic dysfunction without any effect on systolic function in MS rats. In the present study, the experimental results showed that nitric oxide (NO) production and superoxide dismutase (SOD) level decreased while the level of malondialdehyde (MDA) increased in the left ventricular cardiomyocytes of MS rats. After treatment with AST in MS rats, cardiac MDA was attenuated as well as NO production and SOD level were dose-dependently improved. The highest dose of AST (2.0 mg/kg) increased cyclic guanosine monophosphate (cGMP) production in the myocardium. At the mean time, the total endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) expression had no significant changes. Compared with the normal control rats, eNOS dimer was decreased in HFFD induced MS rats. Both low and high dose AST treatments restored the eNOS dimer expression of myocardium in MS rats. Conclusions: The present study demonstrated that AST ameliorated the oxidative stress damage and metabolic abnormalities in HFFD induced MS rats. The antioxidant properties of AST and its protection function of the left ventricular diastolic function worked through the eNOS/NO/cGMP pathway.