暖心康基于ACLY调控成纤维细胞激活防治心力衰竭心肌纤维化OA

Objective To investigate whether Nuanxinkang inhibits cardiac fibroblast activation and improves myocardial fibrosis in heart failure mice by regulating the expression of ATP-citrate lyase(ACLY).Methods Forty 6-week-old male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,Nuanxinkang group(1.65 g·kg-1),and Entresto group(Sacubitril Valsartan Sodium,60 mg·kg-1).A mouse model of chronic heart failure was established via transverse aortic constriction(TAC).After 6 weeks of treatment,the effects of Nuanxinkang on cardiac function and myocardial fibrosis in TAC mice were comprehensively evaluated.Echocardiography was performed to assess cardiac function parameters,including left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS).Masson's trichrome staining was used to observe the level of myocardial fibrosis,while hematoxylin and eosin(HE)staining was employed to evaluate inflammatory infiltration in myocardial tissues.Quantitative real-time PCR(qPCR)was utilized to detect the mRNA expression levels of fibrosis-related genes,such as Fibronectin,Collagen 1,Collagen 3,α-SMA,FSP1,and Vimentin.Western Blot(WB)was conducted to measure the protein expression of Collagen 1,ATP-citrate lyase(ACLY),and Vimentin.Furthermore,immunofluorescence(IF)staining was performed to assess the expression and co-localization of ACLY and PDGFRα in cardiac tissues.Results Compared with the sham group,the model group exhibited significantly decreased LVEF and LVFS(P＜0.01),accompanied by disordered arrangement of myocardial fibers,increased collagen deposition(P＜0.01),and elevated levels of inflammatory infiltration(P＜0.01).The mRNA expression levels of Fibronectin,Collagen 1,and Collagen 3,as well as Collagen 1 protein expression,were significantly increased(P＜0.01).Furthermore,the protein expression of ACLY and PDGFRα(P＜0.01),along with their co-localization area(P＜0.01),was upregulated in the model group.Additionally,the protein expression of Vimentin and the mRNA levels of α-SMA,Vimentin,and FSP1 were significantly elevated(P＜0.01).Compared with the model group,both the Nuanxinkang group and the Entresto group showed significant improvements in cardiac function,characterized by markedly increased LVEF and LVFS(P＜0.01).These treatment groups also exhibited reduced collagen deposition(P＜0.01)and inflammatory infiltration(P＜0.05,P＜0.01).The protein expression of Collagen 1 and the mRNA levels of Fibronectin,Collagen 1,and Collagen 3 were significantly downregulated(P＜0.05,P＜0.01).Moreover,the protein levels of ACLY and PDGFRα,as well as their co-localization area,were significantly decreased(P＜0.05,P＜0.01).Finally,the protein expression of ACLY and Vimentin,along with the mRNA levels of α-SMA,FSP1,and Vimentin,was significantly downregulated(P＜0.01).Conclusion Nuanxinkang effectively ameliorates cardiac dysfunction and myocardial fibrosis in heart failure mice.The underlying mechanism may be associated with the inhibition of cardiac fibroblast activation through suppressing the expression of ACLY.