Kangxian-Yixin Granule alleviates myocardial fibrosis in rats with dilated cardiomyopathy through RhoA/ROCK1 pathway

FASEB JOURNAL(2020)

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摘要
Objective Kangxian‐Yixin granule (KXYX) is an effective traditional Chinese medicine prescription for the clinical treatment of dilated cardiomyopathy (DCM). The purpose of this study was to study the role of RhoA/ROCK1 signaling pathway in DCM myocardial fibrosis and the intervention mechanism of KXYX. Methods DCM rats were randomly divided into model group (n = 8), KXYX group (n = 8), captopril group (n = 8) and control group (n = 8). After 4 weeks of drug intervention, the cardiac function of rats was detected by echocardiography, and the degree of myocardial fibrosis was observed by Masson staining. The expressions of RhoA, ROCK1, p‐MLC and fibrosis related factors CTGF and Col‐1 in RhoA/ROCK1 signaling pathway were detected by PCR and Western blot. At the same time, the myocardial fibroblast model was induced by angiotensin II, and treated with KXYX and inhibitor fasudil. RhoA/ROCK1 signaling pathway and the expression of fibrosis factors CTGF and Col‐1 were detected by Western blot and PCR. Results Compared with the control group, the expression of RhoA/ROCK1 signaling pathway in the model group was up‐regulated, the expression of p‐MLC was overactivated, and the expression of fibrosis‐related factors CTGF and Col‐1 was increased in the model group (P < 0. 05). KXYX could inhibit myocardial fibrosis, inhibit the transformation of fibroblasts into myofibroblasts, and down‐regulate the expression of RhoA/ROCK1 signaling pathway and fibrosis factors CTGF and Col‐1 in DCM rats. Conclusion RhoA/ROCK1 signaling pathway plays an important role in DCM myocardial fibrosis, and KXYX can inhibit the up‐regulation of RhoA/ROCK1 signaling pathway, thus inhibiting the development of myocardial fibrosis in DCM rats. The correspondence to Lihua Han; hlhaa@sina.com . Support or Funding Information This work was financially supported by grants from the National Natural Science Foundation of China (Grant No. 81573920)
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myocardial fibrosis
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