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

Juan Zhao,Hui-Hua Chen,Rong Lu,Chen Zhang,Hong-Chang Wei,Jing Tian,Wei Guo,Tong-Tong Cao

doi:10.1155/2016/4621235

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.

Highlights

Diabetic patients have a 2- to 5-fold increased risk of developing heart failure [1], which is partly driven by diabetic cardiomyopathy (DCM)
The results demonstrated that left ventricular systolic pressure (LVSP) and +dp/dtmax values did not significantly differ between nondiabetic and db/db mice, suggesting unaltered systolic function
Using Masson staining and Collagen Volume Fraction (CVF) quantifiable analysis, we found that db/db mice exhibited more severe myocardial fibrosis compared to nondiabetic mice, indicated by increased blue collagenous fibers and higher CVF values

Summary

Introduction

Diabetic patients have a 2- to 5-fold increased risk of developing heart failure [1], which is partly driven by diabetic cardiomyopathy (DCM). DCM is characterized by diastolic dysfunction, myocardial fibrosis, and hypertrophy without ischemic heart disease, hypertension, or other comorbidities. The pathogenesis of DCM is complicated, but myocardial fibrosis, which increases ventricle stiffness, is thought to be one of the major causes of myocardial dysfunction [2]. Numerous studies demonstrated that one of the key determinants of myocardial fibrosis is the accumulation of increased extracellular matrix (ECM), which causes irreversible tissue damage and consequent cardiac dysfunction, resulting in heart failure [3]. In the present study, we investigated the effects of SMS on cardiac function and fibrosis in a type 2 diabetic db/db mouse model, to further observe the associated signaling mechanism

Methods

Results

Conclusion