Effect of sinomenine on inflammatory response and myocardial fibrosis in rats with atrial fibrillation by regulating the TLR4/NOX4 signaling pathway
Objective To investigate the effect of sinomenine on inflammatory response and myocardial fibrosis in rats with atrial fibrillation by regulating the Toll-like receptor 4(TLR4)/NADPH oxidase 4(NOX4)signaling pathway.Methods SD rats were randomly grouped into control group,model group,sinomenine(20、40、80 mg/kg)group,verapamil group,and sinomenine + Pam3Cys group,with 12 rats in each group.Rats in control group was injected with an equal amount of physiological saline through the sublingual vein instead of atrial fibrillation inducing fluid,rats in other groups were used to construct atrial fibrillation rat models by injecting atrial fibrillation inducing fluid into the sublingual vein.After successful modeling,medication was administered once daily for 2 weeks.Color doppler ultrasound was applied to detect changes in left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS)in rats.ELISA method was applied to detect the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat serum.The left ventricular mass index of rats was detected,HE staining was applied to detect pathological changes in rat myocardial tissue,Masson staining was applied to detect the degree of myocardial fibrosis in rats,qRT-PCR was applied to detect the expression of transforming growth factor-β1(TGF-β 1)and Collagen-I mRNA in left ventricular myocardial tissue.Western blotting was applied to detect the expression of TLR4 and NOX4 proteins in rat left ventricular myocardial tissue.Results Compared with the model group,the myocardial tissue pathological damage and severe myocardial fibrosis of rats in sinomenine group were improved,LVEF and LVFS were increased,the IL-6 and TNF-α levels,TGF-β 1 and Collagen-Ⅰ mRNA expression,and TLR4,NOX4 protein expression were reduced(P<0.05).Compared with sinomenine group,the myocardial tissue pathological damage and myocardial fibrosis of rats in sinomenine + Pam3Cys group were aggravated,LVEF and LVFS were reduced,IL-6 and TNF-α levels,TGF-β 1 and Collagen-Ⅰ mRNA expression,and TLR4,NOX4 protein expression were increased(P<0.05).Conclusion Sinomenine may inhibit inflammatory response and myocardial fibrosis in rats with atrial fibrillation by inhibiting the TLR4/NOX4 pathway.
NETL
NSTL
万方数据
