Expression and effect of HMGB1 and its inflammatory signaling pathway in ratmodel of DCM / 重庆医学

ABSTRACT

Objective To investigate the expression and effect of high mobility group box 1(HMGB1) and its signaling pathway(HMGB1 RAGE/TLR4-NF-κB-cytokines)in rats with dilatd cardiomyopathy(DCM).Methods The rats were divided into two groups:normal control group (control,n=20) which treated with physiological saline,and DCM group(n=22) which treated with adriamycin(1 mg/kg twice a week)for 6 weeks,and then observed for 2 weeks.Echocardiography was performed at the end of the study.Plasma IL-1,IL-6,TNF-α level were measured by the flow cytometry.The CRP,BNP concentrations were measured by enzyme linked immunosorbent assay (ELISA).The expression of HMGB1 mRNA,TLR4 mRNA,RAGE mRNA,NF κB mRNA were measured by real time PCR.Results There were four rats dead in the DCM group;two rats were randomly selected from the DCM group to certified modeled successfully by echocardiography and pathological examination.Left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) in DCM group were significantly higher than those in the normal control group(P＜0.05);left ventricular ejection fraction (LVEF),left ventricular short axis contractility(FS) in DCM group was significantly lower than that in normal control group(P＜0.05).The expression of H MGB1 mRNA,TLR4 mRNA,RAGE mRNA and NF-κB mRNA in myocardial tissue were significantly increased in DCM group than in the normal control saline group (P＜ 0.05),The expression of HMGB1 mRNA were positively correlated with TLR4 mRNA,RAGE mRNA and NF κB mRNA(r=0.873,P=0.005;r=0.949;P=0.000;r=0.898,P=0.002).The serum levels of IL-1,IL 6,TNF α and CRP were significantly higher in DCM group.The expression of HMGB1 mRNA in myocardial tissue was positively correlated with IL 1,IL-6,TNF-α and CRP(r=0.944,P=0.002;r=0.988,P=0.000;r=0.968,P=0.000;r=0.961,P=0.000).Conclusion HMGB1 and it's inflammation signaling pathway (HMGB1-TLR4/RAGE-NF-κB-cytokines) were highly expressed in dilated cardiomyopathy,and have relationship with left ventricular diameter and cardiac function,they may be involved in the development of DCM.