Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.

Wenjuan Liu,Meng Wang,Wei Gong,Yeping Yang,Xuanchun Wang,Zhaoyun Zhang,Linuo Zhou,Yemei Liu,Meng Wu,Fei Sun,Yifei Yu,Shizhe Guo,Yiming Li,Shengmei Qin,Min He

doi:10.1155/2018/9232065

Abstract

Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-β1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.

Highlights

Diabetic cardiomyopathy (DCM), which was first described by Rubler et al in 1972 [1], is used to refer to ventricular dysfunction in patients with diabetes that is out of proportion to their underlying vascular disease [2]
In a STZ-induced diabetic rat model, here we demonstrate that SPR protects diabetic cardiomyopathy mainly through reducing cardiac fibrosis, oxidative stress, and inflammation, as well as improving mitochondrial dysfunction
Our results demonstrated that there was fibrosis in the STZ + NS group, which further supported the existence of DCM in this STZ-induced rodent model

Summary

Introduction

Diabetic cardiomyopathy (DCM), which was first described by Rubler et al in 1972 [1], is used to refer to ventricular dysfunction in patients with diabetes that is out of proportion to their underlying vascular disease [2]. In 2014, it was estimated that the cumulative probability of death among patients with DCM was 18%, and the incidence of heart failure was 22% [3]. It is well accepted that multiple pathogeneses are involved in the development of DCM, including mitochondrial dysfunction, impaired calcium handling, increased oxidative stress, endothelial dysfunction, and remodeling of the extracellular matrix [2]. Mitochondrial dysfunction is related to decreased energy productivity [5], increased cellular oxidative stress [6, 7], impaired calcium handling [8], and impaired mitochondrial dynamics and biogenesis [9, 10]

Methods

Results

Conclusion