The Effect of Astragalus Polysaccharides on Myocardial Injury in Rats with Experimental Autoimmune Myocarditis by Regulating HMGB1-RAGE Signaling Pathway
Objective:To investigate the effect of astragalus polysaccharides(AP)on myocardial injury in rats with experimental autoimmune myocarditis(EAM)by regulating high mobility group Box-1-receptor for advanced glycation end products(HMGB1-RAGE)signaling pathway.Methods:Totally 50 rats were fed adaptively for one week and randomly separated into control group,EAM group,AP group(30 g/kg),rHMGB1 group(8 µg/kg),and AP+rHMGB1 group[AP(30 g/kg)+rHMGB1(8 μg/kg)].Except for the control group(Freund's complete adjuvant),other groups established EAM rat models by subcutaneous injection of antigen adjuvant emulsion into the left and right hind foot pads,and intervened according to the above dosage.After three weeks,ultrasound was applied to detect heart rate(HR),left ventricular ejection fraction(LVEF)and end-diastolic diameter(LVEDs).Enzyme-linked immunosorbent(ELISA)was applied to detect the levels of inflammatory factors in the serum of rats in each group.Masson's and Hematoxylin-eosin(HE)staining were applied to detect myocardial tissue fibrosis and pathological changes.Western blotting and real-time fluorescence quantitative PCR(qRT-PCR)were applied to detect the protein and mRNA expression of HMGB1 and RAGEA.Results:Com-pared with control group,the EAM group showed severe myocardial structural disorder and fibrosis.And the pathological score,levels of TNF-α and IL-6,HR,LVEDs,and protein and mRNA expression of HMGB1,RAGE obviously increased in EAM group,while LVEF obviously decreased in EAM group(P＜0.05).Compared with EAM group,the pathological damage and fibrosis were improved in AP group.And the pathological score,levels of TNF-α and IL-6,HR,LVEDs,and protein and mRNA expression of HMGB1,RAGE obvi-ously decreased in AP group,while LVEF obviously increased in AP group(P＜0.05).However,the pathological damage and fibrosis further worsened in rHMGB1 group.And the pathological score,levels of TNF-α and IL-6,HR,LVEDs,and protein and mRNA expression of HMGB1.RAGE obviously increased in rHMGB1 group,while LVEF obviously decreased in rHMGB1 group(P＜0.05).Compared with AP group,the pathological damage and fibrosis were slightly aggravated in AP+rHMGB1 group.And the pathological score,levels of TNF-α and IL-6,HR,LVEDs,and protein and mRNA expression of HMGB1,RAGE obviously increased in AP+rHMGB1 group,while LVEF obviously decreased in AP+rHMGB1 group(P＜0.05).Compared with rHMGB1 group,the pathological damage and fibrosis were improved in AP+rHMGB1 group.And the pathological score,levels of TNF-α and IL-6,HR,LVEDs,and protein and mRNA expression of HMGB1,RAGE obviously decreased in AP+rHMGB1 group,while LVEF obviously increased in AP+rHMGB1 group(P＜0.05).Conclusion:AP may improve myocardial injury in EAM rats by inhibiting HMGB1-RAGE signaling pathway.
万方数据
维普
