摘要
目的探究高迁移率族蛋白B1(HMGB1)对葡聚糖硫酸钠(DSS)诱导的炎症性肠病(inflammatory bowel disease,IBD)小鼠模型中氧化应激的影响及其机制。方法将小鼠分为对照组、DSS组、HMGB1重组蛋白(rhHMGB1)组和甘草酸组,每组6只。对照组小鼠正常饲养,DSS组小鼠自由饮用5%的DSS溶液6 d诱导IBD模型,rhHMGB1组和甘草酸组小鼠在IBD模型构建前,分别腹腔注射50μg/kg rhHMGB1和50μg/kg甘草酸。HE染色观察小鼠结肠病理形态,qRT-PCR和Western blot检测小鼠结肠组织HMGB1的表达,试剂盒检测小鼠结肠组织中谷胱甘肽(GSH)和丙二醛(MDA)含量,Western blot检测小鼠结肠组织核因子红细胞相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、谷胱甘肽过氧化物酶4(GPX4)的蛋白表达。结果与对照组比较,DSS组小鼠结肠出现病理损伤,HMGB1 mRNA和蛋白表达均上调(P<0.01),MDA水平增加(P<0.01),GSH水平下降,Nrf2、HO-1和GPX4表达下调(P<0.01)。与DSS组比较,rhHMGB1组小鼠结肠病理损伤加重,HMGB1 mRNA和蛋白表达上调(P<0.01),MDA水平增加(P<0.01),GSH水平下降,Nrf2、HO-1和GPX4表达下调(P<0.01)。与DSS组和rhHMGB1组比较,甘草酸组小鼠结肠病理损伤减轻,HMGB1 mRNA和蛋白表达下调(P<0.01),MDA水平下降(P<0.01),GSH水平增加,Nrf2、HO-1和GPX4表达上调(P<0.01)。结论HMGB1的表达被抑制后,NRF2/HO-1/GPX4轴激活,进而影响IBD小鼠体内过度的氧化应激反应,减轻结肠病理损伤。
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 50μg/kg rhHMGB1 and 50μg/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.
作者
陈小红
田霞
CHEN Xiaohong;TIAN Xia(Department of Gastroenterology,Wuhan Third Hospital,Wuhan 430060,China)
出处
《山西医科大学学报》
CAS
2024年第3期326-331,共6页
Journal of Shanxi Medical University
基金
武汉市卫生健康委科研基金资助项目(WX21Q13)。
作者简介
陈小红,女,1989-09生,博士,主治医师,E-mail:15071179645@126.com;通讯作者:田霞,E-mail:tianxia20190823@163.com。
