Effects Of Astragaloside â…£ On Isoproterenol-induced Cardiac Hypertrophy And The Underlying Mechanism

Objective To observe the protective effect of Astragaloside IV on isoproterenol induced cardiac hypertrophy and explore the underlying mechanism in the view of energy biosynthesis.Methods(1)In vivo experiment: 30 male rats were randomly divided into 3 groups: Control group, Model group and Astragaloside IV group. The rats in Astragaloside IV group was ig administered with Astragaloside IV(80 mg · kg-1· d-1) for 1 days before ip injection with isoproterenol(10 mg· kg-1·d-1) for another 2 weeks.(2) In vitro experiment: The primary ventricular myocytes of neonatal rats were cultured and divided into 4 groups: Control group, Model group, Parthenolide(Par, NF-κB inhibitor) group and Astragaloside IV group. The cells in Par and Astragaloside IV groups were incubated with ASIV and Par respectively for 30 minutes before the treatment with isoproterenol(10μM) for 48 h.(3) Small RNA interference: Cells were assigned to 4 groups: si RNA Control group, Model group, p65 si RNA group. The heart mass index(HMI), left ventricular mass index(LVMI) were measured; The heart tissues were taken for hematoxylin-eosin(HE) staining and histological analysis; Cell surface area were analyzed by the microphotograph; Total protein contents were assayed by the method of Bradford; Real time RT-PCR was used to quantify the m RNA expression of ANP and BNP; ELISA was used to analyze the content of free fatty acids(FFA), adenosine triphosphate(ATP), adenosine diphosphate, adenosine monophosphate(AMP); Western blotting was used to quantify p65 and PGC-1α protein expression.Results(1) In vivo and vitro: In vivo, compared with the Control group, the heart mass index(HMI), left ventricular mass index(LVMI) and cell surface area increased significantly in isoproterenol-induced model rats. In vitro, compared with the Control group, the Model group show significant increment of total protein content and cell surface area. Both in vivo and vitro, compared with the Control group, the levels of ANP, BNP m RNA and FFA content increased, ATP/AMP ratio decreased obviously in Model group. In addition, the amount of p65 protein decreased in cytoplasm, increased in nuclear fraction significantly and PGC-1α protein expression decreased remarkably in Model group. However, Astragaloside IV could reverse these changes(P < 0.05).(2) Small RNA interference experiment: Compared with Model, PGC-1α protein expression increased in p65 si RNA group.Conclusions Astragaloside IV can effectively reverse isoproterenol-induced cardiac hypertrophy, reduce the accumulation of FFA and increase the energy supply, which plays a role of cardiac protective. Astragaloside IV can significantly reduce the translocation of NF-κB into nuclear fraction induced by isoproterenol. The underlying protective mechanism of Astragaloside IV may partly attributed to NF-κB/ PGC-1α signaling pathway, thereby regulating the key molecules involved in energy biosynthesis and ameliorating Iso-induced cardiac hypertrophy.