Abstract
Objective:To investigate the mechanism of icariin(ICA)on improving cardiac function in mice with chronic heart failure(CHF)and its effect on gene expression of Toll-like receptor 4(TLR4)signaling pathway.Methods:Transverse aortic constric-tion was used to reproduce the CHF mouse model,low(ICA-L)and high(ICA-H)doses of ICA were used to intervent.Lipopolysac-charide(LPS),a TLR4 signal specific agonist,was used as a functional rescue test.High-resolution small animal ultrasound imaging system was used to detect left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic diameter(LVIDd),left ventric-ular ejection fraction(LVEF)and left ventricular short axis shortening(LVFS).TUNEL staining was used to detect apoptosis of myo-cardial tissue of mice in each group.Immunofluorescence was used to detect expressions of TNF-α and IL-6.qRT-PCR was used to detect mRNA expressions of TLR4,high mobility group box 1(HMGB1),myeloid differentiation factor 88(MyD88)and nuclear factor κB(NF-κB).Western blot was used to detect protein expressions of TLR4,HMGB1,MyD88 and phosphorylated NF-κB(p-NF-κB).Results:Compared with Sham group,LVIDd and LIVDs,apoptosis rate of myocardial tissue,immunofluorescence intensity of TNF-α and IL-6 in myocardial tissue,mRNA expressions of TLR4,HMGB1,MyD88,NF-κB and protein expressions of TLR4,HMGB1,MyD88 and p-NF-κB in myocardial tissue were significantly increased,while LVEF and LVFS were significantly decreased in CHF group,ICA-L group,ICA-H group and ICA-H+LPS group.Compared with CHF group,LVIDd and LIVDs,apoptosis rate of myocardial tissue,immunofluorescence intensity of TNF-α and IL-6 in myocardial tissue,mRNA expressions of TLR4,HMGB1,MyD88,NF-κB,and protein expressions of TLR4,HMGB1,MyD88 and p-NF-κB in myocardial tissue were significantly decreased,while LVEF and LVFS were significantly increased in ICA-L group,ICA-H group and ICA-H+LPS group.Compared with ICA-L group,LVIDd and LIVDs,apoptosis rate of myocardial tissue,immunofluorescence intensity of TNF-α and IL-6 in myocardial tissue,mRNA expres-sions of TLR4,HMGB1,MyD88,NF-κB,and protein expressions of TLR4,HMGB1,MyD88 and p-NF-κB in myocardial tissue were significantly decreased,while LVEF and LVFS were significantly increased in ICA-H group.Compared with ICA-H group,LVIDd and LIVDs,apoptosis rate of myocardial tissue,immunofluorescence intensity of TNF-α and IL-6 in myocardial tissue,mRNA expressions of TLR4,HMGB1,MyD88,NF-κB,and protein expressions of TLR4,HMGB1,MyD88 and p-NF-κB in myocardial tissue were significantly increased,while LVEF and LVFS were significantly decreased in ICA-H+LPS group(P<0.05),there was no statistically significant difference in expression of NF-κB in myocardial tissues of mice in each group(P>0.05).Conclusion:ICA can significantly inhibit inflammatory stress and collagen deposition in CHF mice,reduce apoptosis rate of myocardial tissue,and improve the cardiac function of experimental animals,which may be related to the inhibition of TLR4 signaling pathway.关键词
淫羊藿苷/慢性心力衰竭/心功能/Toll样受体4信号通路Key words
Icariin/Chronic heart failure/Cardiac function/Toll-like receptor 4 signaling pathway分类
医药卫生
