Effect of HMGB1 in oxidative stress injury on inflammatory bowel disease and its mechanism
Objective To investigate the effect and mechanism of high mobility group protein B1(HMGB1)on oxidative stress in mouse of inflammatory bowel disease(IBD)induced by dextran sulphate sodium(DSS).Methods The mice were divided into control group,DSS group,HMGB1 recombinant protein(rhHMGB1)group and glycyrrhizic acid group,with 6 mice in each group.The mice in control group were fed normally.The mice in DSS group drank 5％DSS solution freely for 6 d to induce the IBD model.The mice in rhHMGB1 group and glycyrrhizic acid group were intraperitoneally injected with 50 μg/kg rhHMGB1 and 50 μg/kg glycyrrhizic acid before the establishment of IBD model,respectively.The pathological morphology of colon was observed by HE staining.The expression of HMGB1 in colon tissues of mice was detected by qRT-PCR and Western blot.The contents of glutathione(GSH)and malondialdehyde(MDA)in colon tissues of mice were detected by the kit.The protein expressions of erythrocyte associated factor 2(Nrf2),heme oxygenase-1(HO-1),glutathione peroxidase 4(GPX4)in colon tissue of mice were detected by Western blot.Results Compared with control group,GSH level,mRNA and protein expressions of HMGB1,and expressions of Nrf2,HO-1,GPX4 were decreased in DSS group(P＜0.01),the pathological injury of colon was found,and MDA level was increased(P＜0.01).Compared with DSS group,GSH level,mRNA and protein expressions of HMGB1,and expressions of Nrf2,HO-1,GPX4 were decreased in rhHMGB1 group(P＜0.01),the pathological injury of colon was aggravated,and MDA level was increased in rhHMGB1 group(P＜0.01).Compared with DSS group and rhHMGB1 group,GSH level,mRNA and protein expressions of HMGB1,and expressions of Nrf2,HO-1,GPX4 were decreased in glycyrrhizic acid group(P＜0.01),the pathological injury of colon was reduced,and MDA level was increased in glycyrrhizic acid group(P＜0.01).Conclusion Downregulation of HMGB1 expression can activate the NRF2/HO-1/GPX4 axis,thereby affecting excessive oxidative stress in IBD mice,which attenuates colonic pathological damage.
inflammatory bowel diseasehigh mobility group protein B1nuclear factor erythrocyte associated factor 2/heme oxygenase-1/glutathione peroxidase 4 axisoxidative stresscolonic injury
万方数据
维普
