Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice

Abstract

In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-β dependent pathway.