心脑血管病防治2024，Vol.24Issue(3)：5-10,63,封3,8.DOI:10.3969/j.issn.1009-816x.2024.03.002
金雀异黄酮通过Toll样受体4信号通路改善急性心肌梗死大鼠左心室功能的研究
Improvement of left ventricular function in rats with acute myocardial infarction through Toll-like receptor 4 signaling pathway by genistein
摘要
Abstract
Objective To explore the effect and potential mechanism of genistein(GEN)on left ventricular function in rats with acute myocardial infarction(AMI)based on Toll-like receptor 4(TLR4)signaling pathway.Methods One hundred male SD rats were randomly divided into sham operation group,model group,GEN(40 mg/kg)group,GEN+TAK242(TLR4 inhibitor,10 mg/kg)group,and GEN+LPS(TLR4 activator,5 mg/kg)group,with 20 rats in each group.The AMI rat model was established by ligation of the left anterior descending coronary artery.After intragastric administration once a day for 4 weeks,left ventricular function was detected by cardiac ultrasound.The levels of angiotensin Ⅱ(Ang Ⅱ),stromal lysin 2(ST2),and brain natriuretic peptide(BNP)in serum were determined by enzyme linked immunosorbent assay(ELISA).Left ventricular mass index(LVMI)was calculated,and histopathological changes in left ventricular myocardial tissue were observed by hematoxylin-eosin(HE)staining.Fibrosis in left ventricular myocardial tissue was observed by Masson staining,and the collagen volume fraction(CVF)was calculated.The levels of tumor necrosis factor(TNF)-α,interleukin-1β(IL-1β),IL-6 in left ventricular myocardial tissue were determined by ELISA.Protein expression of TLR4,nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,transforming growth factor-β1(TGF-β1),Collagen(Col)-Ⅰ,Col-Ⅲ,α-smooth muscle actin(α-SMA)was detected by Western blot.Results Compared with the model group,the heart function in GEN group was significantly improved,left ventricular internal diameter at end-systolic(LVIDs)and left ventricular internal diameter at end-diastolic(LVIDd)reduced,left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF)increased;serum levels of AngⅡ,ST2,BNP,and LVMI were decreased;pathological changes and fibrosis of left ventricular myocardial tissue were significantly improved,CVF was decreased;the levels of TNF-α,IL-1β,IL-6 in myocardial tissue were decreased;the expression of TLR4,TGF-β1,Col-Ⅰ,Col-Ⅲ,α-SMA and the ratio of p-NF-κB p65/NF-κB p65 were decreased,the differences were statistically significant(P＜0.05).TAK242 significantly enhanced the regulatory effect of GEN on the above indexes in AMI rats,while LPS blocked the regulatory effect of GEN on the above index in AMI rats.Conclusion GEN can inhibit ventricular remodeling and improve left ventricular function in AMI rats.Its mechanism may be related to the inhibition of TLR4 signaling pathway,alleviation of inflammatory reaction,and reduction of extracellular matrix formation.关键词
急性心肌梗死/金雀异黄酮/TLR4信号通路/炎症/细胞外基质Key words
Acute myocardial infarction/Genistein/Toll-like receptor 4 signaling pathway/Inflammation/Extracellular matrix引用本文复制引用
姚飞,郭云亢,张丽娜..金雀异黄酮通过Toll样受体4信号通路改善急性心肌梗死大鼠左心室功能的研究[J].心脑血管病防治,2024,24(3):5-10,63,封3,8.基金项目
河北省医学科学研究课题(20210854) （20210854）
