Spirolactone provides protection from renal fibrosis by inhibiting the endothelial–mesenchymal transition in isoprenaline-induced heart failure in rats

Drug Design, Development and Therapy

关键词: spironolactone;    heart failure;    renal fibrosis;    transforming growth factor;    endothelial-mesenchymal transition;   

DOI  :  

来源: DOAJ

【 摘 要 】

Hao Zhou, Dan Xi, Jichen Liu, Jinjin Zhao, Si Chen, Zhigang GuoDivision of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaBackground: Fibrosis results in excessive accumulation of extracellular matrix proteins, collagen component alteration, and abnormalities in structure and is partly derived from a process called the endothelial–mesenchymal transition involving transforming growth factor β (TGF-β). We investigated whether spironolactone, an aldosterone receptor blocker, attenuated isoprenaline (Iso)-induced heart failure in rats and also studied the mechanism for the same.Methods: Sprague–Dawley rats were subcutaneously injected with Iso to induce heart failure, which promoted renal fibrosis; rats with spironolactone treatment were given a gavage of spironolactone (30 or 60 mg/kg/d, for 21 days). Cardiac function and fibrosis indices were measured. Pathological alterations and expression of Type I and III collagen, α-smooth muscle actin, cluster of differentiation-31, and TGF-β were examined.Results: In Iso-induced heart failure in rats, spironolactone significantly improved cardiac function and decreased myocardial fibrosis, reduced collagen fibrous proliferation in kidney, reduced expression of Type I and III collagen, increased the expression of cluster of differentiation-31, and decreased the expression of α-smooth muscle actin and TGF-β.Conclusion: Spironolactone may prevent renal fibrosis by inhibiting the endothelial–mesenchymal transition.Keywords: spironolactone, heart failure, renal fibrosis, endothelial–mesenchymal transition

【 授权许可】

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