Improvement of left ventricular function in rats with acute myocardial infarction through Toll-like receptor 4 signaling pathway by genistein
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.
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