The Effect of DNMT1 on Myocardial Fibrosis in Rats with Chronic Heart Failure Models

CHENG Na; HAN Jing; SHAN Zimei

doi:10.12102/j.issn.1672-1349.2025.14.009

Abstract：Objective:To explore the effect of DNA methyltransferase 1(DNMT1)on myocardial fibrosis in rats with chronic heart failure(CHF)models and its molecular mechanism.Methods:The SD rats were randomly divided into Sham operation(Sham)group,CHF group,si-NC group and si-DNMT1 group.Except for the Sham group,the CHF models were replicated through abdominal aortic coarctation.The abdominal aorta of the rats in the Sham group was isolated but not ligated.After the operation,the si-NC group and the si-DNMT1 group were injected with negative control lentivirus and DNMT1 siRNA recombinant lentivirus through myocardium injection respectively.The left ventricular ejection fraction(LVEF),left ventricular shortening rate(LVFS),left ventricular end-diastolic diameter(LVEDD),and left ventricular end-systolic diameter(LVESD)of rats in each group were determined by Doppler ultrasound.The histopathological changes of myocardial tissues of rats in each group were observed by hematoxylin-eosin(HE)staining.Masson staining was used to observe the myocardial tissue fibrosis.The expression of α-smooth muscle actin(α-SMA)in myocardial tissues of rats were detected by immunofluorescence staining.The expression levels of Collagen Ⅰ and Collagen Ⅲ in myocardial tissues of rats were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)and Western Blot.Results:Compared with the Sham group,the relative expression levels of DNMT1 mRNA and protein in the myocardial tissue of CHF group were upregulated(P＜0.05),LVEF and LVFS decreased(P＜0.05),LVEDD and LVESD increased(P＜0.05),and the arrangement of myocardial cells was disordered,with necrosis or degeneration.The blue-stained fibrous tissue was significantly more abundant,CVF increased(P＜0.05),the expression of α-SMA labeled with red fluorescence increased(P＜0.05),and the relative expressions of Collagen Ⅰ and Collagen Ⅲ mRNA and protein significantly upregulated(P＜0.05).Compared with the CHF group,the LVEF and LVFS of rats in the si-DNMT1 group increased(P＜0.05),LVEDD and LVESD decreased(P＜0.05),myocardial cell injury improved,blue-stained fibrous tissue was reduced,CVF decreased(P＜0.05),and the expression of α-SMA labeled with red fluorescence decreased(P＜0.05).The relative expressions of Collagen Ⅰ and Collagen Ⅲ mRNA and protein both down-regulated(P＜0.05).Conclusion:The expression of DNMT1 increased in the myocardial tissue of CHF model rats.Inhibition of DNMT1 expression could improve myocardial fibrosis and exert some protective effect on cardiac function.