Effects of Xinkang Granule(康冲剂)on Myocardial Fibrosis in Rats of Chronic Heart Failure Based on LncGAS5/DNMT3A Pathway
Objective To investigate the mechanism of Xinkang Granule(心康冲剂)regulating long non-coding RNA growth arrest specific transcript 5(LncGAS5)/DNA methyltransferase 3A(DNMT3A)pathway against myocardial fibrosis in rats with chronic heart failure.Methods Among 62 SD rats,6 rats were randomly selected as the normal group,and the remaining 56 rats were intraperitoneally injected with adriamycin to establish the chronic heart failure model.The 52 rats successfully modeled were randomly divided into the model group(12 rats,injected with PBS+normal saline by gavage),GAS5 silence group(10 rats,injec-ted with AAV9-GAS5-RNAi+normal saline by gavage),negative control group(10 rats,injected with AAV NC+normal sa-line by gavage),Xinkang Granule group(10 rats,injected with AAV9-GAS5-RNAi+Xinkang Granule solution by gavage)and Valsartan group(10 rats,injected with AAV9-GAS5-RNAi+Valsartan solution by gavage).After treatment,the cardiac func-tion of each group was detected by cardiac ultrasound.Masson staining was used to observe the morphology of heart tissue.The expression of left ventricular fibrosis protein α-SMA in each group was detected by immunofluorescence staining.Serum Col Ⅰexpression was detected by enzyme-linked immunosorbent assay.lncGAS5 and DNMT3A mRNA were detected by Real-time PCR.The protein expression levels of DNMT3A,phosphatase and tensin homolog deleted on chromosome ten(PTEN)and phos-phorylated protein kinase B(AKT)were detected by Western blot.Results Compared with those of the blank group,the values of left ventricular ejection fractions(LVEF)and left ventricular fractional shortening(LVFS)in the model group were significantly decreased(P＜0.05).The staining results showed serious myocardial fibrosis.Col Ⅰ levels in blood were increased significantly(P＜0.05).lncGAS5 mRNA expression was decreased,DNMT3A mRNA and protein expression was increased,PTEN protein expression was decreased and AKT protein expression was increased(P＜0.05).Compared with the of the model group,the stai-ning or index results of GAS5 silencing group were further decreased or increased.Compared with that of the GAS5 silencing group,the staining results showed that myocardial fibrosis was alleviated after intervention of Xinkang Granule and valsartan,and the values of LVEF and LVFS were increased to varying degrees(P＜0.05).Col Ⅰ levels in serum were decreased.lnc-GAS5mRNA expression increased and DNMT3A mRNA expression decreased.The protein expressions of DNMT3A and AKT were decreased,while the protein expressions of PTEN were increased(P＜0.05).Conclusion Xinkang Granule can improve the cardiac function of rats with chronic heart failure by regulating LncGAS5/DNMT3A/PTEN/AKT pathway and downstream fibrosis factors,thereby improving myocardial fibrosis in rats with chronic heart failure.
万方数据
维普
