Kangxianyixin Granule Improves Myocardial Fibrosis by Suppressing RhoA/ROCK1 Pathway

Abstract

Background: Kangxianyixin granule (KXYX), a traditional Chinese medicine prescription, has been clinically used to treat dilated cardiomyopathy (DCM) for many years. Myocardial fibrosis (MF) is a major pathological feature of DCM and independent predictor of adverse cardiac outcomes. The present study investigated the effect and the possible mechanism of KXYX on myocardial fibrosis. Methods: Male wistar rats of DCM was induced by furazolidone (Fz) (0.3 mg/g/day, gavage) for 8 weeks and treated with KXYX (3.6, 1.8, 0.9 g/kg/day) or captopril for another 4 weeks. The cardiac function indices were evaluated using ECHO. Myocardial morphology was visualized using H&E and masson staining. Then, the effect of differentiation of Ang II-induced cardiac fibroblasts (CFs) to myofibroblasts was detected using a-SMA and Vimentin immunohistochemical staining. The expression of RhoA, ROCK1, p-MLC were observed using western blot. The mRNA level of RhoA, ROCK1, MLC were assayed by quantitative RT-PCR. Result: Fz-induced rats had changes in the structure and function of the left ventricle as well as myocardial fibers broken and loosely arranged, cardiomyocytes necrosis in the myocardial tissue. High level expressions of fibrosis were observed in the model rats. The expressions of RhoA, ROCK1, p-MLC were elevated in dilated heart and Ang Ⅱ-induced CFs, while KXYX can rescued cardiac dysfunction and remodeling, inhibited the process of MF and down-regulated RhoA/ROCK1 signaling which suppressed the differentiation of fibroblasts into myofibroblasts. Conclusion: Our study demonstrated that KXYX attenuated the development of myocardial fibrosis by down-regulating the expression of RhoA/ROCK1 signaling pathway in vivo and vitro. Thus, we provided an underlying mechanism of KXYX function in DCM therapy.