Effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect

Aim： To study the effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect. Method： Ventricular remodeling in mice was induced by consecutively subcutaneous injection of isoproterenol for 14 days.Astragaloside IV(40，80 mg/kg) and propranolol(40 mg/kg，positive control) were administered by gavage to mice.Echocardiography was used to observe the left ventricular end diastolic diameter(LVIDd)，left ventricular end systolic diameter(LVIDs)，fractional shortening(FS) and ejection fraction(EF).The myocardial pathological pattern was detected by HE staining.Expressions of matrix metalloproteinases(MMP2，MMP9) and tissue inhibitor of metalloproteinases(TIMP1，TIMP2) mRNA in myocardium were detected by RT-PCR.Activities of MMP2 and MMP9 were assayed by zymography. Results： Compared with those of control mice，LVIDd and LVIDs were increased，FS and EF were decreased in the model group.Myocardial injury and fibrosis existed in histop at hological slices of the model group.In addition，the mRNA expressions and activities of MMP2 and MMP9 were increased in the model group.However，there were no markable changes to TIMP1 and TIMP2.Treatment with astragaloside IV reduced LVIDd and LVIDs，increased FS and EF，attenuated myocardial injury，and down-regulated mRNA expressions and activities of MMP2 and MMP9 compared with the model group. Conclusion： Astragaloside IV can greatly improve ventricular remodeling and dysfunction via decreasing MMP2 and MMP9 mRNA expression and activities in cardiac ventricles.