The Effect Of Kangxian-Yixin Decotion On Myocardial Fibrosis In Dilated Cardiomyopathy Rats Based On MicroRNAs

Objective:To explore the mechanism of Kangxian-Yixin Decoction on myocardial fibrosis in dilated cardiomyopathy(DCM)animal model and myocardial fibrosis cell model from the perspective of microRNAs.Method:1.The model of myocardial fibrosis in DCM rats was established by using furazolidone(FZD)and verified by echocardiography,Masson staining and α-SMA.The differentially expressed microRNAs were screened by qPCR arrays and verified in DCM animal model.2.AngⅡ was used to prepare myocardial fibrosis cell model,and the optimal intervention concentration of Kangxian-Yixin Decoction was determined.The expression level of α-SMA was detected by Western blot,and the differentially expressed microRNAs screened from the above DCM animal models were verified.Objective to study the mechanism of anti fibrosis and Kangxian-Yixin Decoction on myocardial fibrosis by silencing differentially expressed microRNAs by adenovirus.Result:1.In DCM myocardial fibrosis model rats,the myocardial interstitial space increased,LVESD and LVEDD increased,EF decreased,α-SMA expression increased,KangxianYixin Decoction had obvious intervention effect(P<0.05 or P<0.01).2.qPCR arrays detected 80 differentially expressed microRNAs related to heart disease,and the expression trend of 60 microRNAs was statistically significant.In addition,miR-125b-5p was selected as the further research object based on the analysis of pathway and differential target genes.3.The results showed that the expression of miR-125b-5p in the model group was upregulated(2.835±0.244).Kangxian-Yixin Decoction could significantly down regulate the expression of miR-125b-5p(0.641±0.068,P<0.05).4.AngⅡ exposure significantly increased the levels of α-SMA and miR-125b-5p in myocardial fibrosis cells.Kangxian-Yixin Decoction(0.18 mg/ml)significantly decreased the levels of α-SMA and miR-125b-5p(P<0.05 or P<0.01).5.AngⅡ exposure significantly increased the levels of α-SMA and miR-125b-5p in myocardial fibrosis cells.Kangxian-Yixin Decoction(0.18 mg/ml)significantly decreased the levels of α-SMA and miR-125b-5p(P<0.05 or P<0.01).Conclusion:1.Kangxian-Yixin Decoction can improve cardiac function of DCM rats;2.Kangxian-Yixin Decoction can reduce the expression of miR-125b-5p and α-SMA in DCM rat model;3.Kangxian-Yixin Decoction can inhibit myocardial fibrosis in rats and cells induced by myocardial fibrosis,which may be related to the down regulation of miR-125b-5p expression.