首页|甘草酸苷调控Nrf2/HO-1信号通路治疗溃疡性结肠炎的机制探究

甘草酸苷调控Nrf2/HO-1信号通路治疗溃疡性结肠炎的机制探究

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目的 探究甘草酸苷(GL)调控核因子红系相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路治疗溃疡性结肠炎(UC)的机制.方法 将HT-29细胞随机分为正常组、模型组和低、中、高GL浓度组.模型组和不同GL浓度组细胞分别加入0.8 mmol/L的H2O2作用于细胞4 h建立氧化应激模型,H2O2刺激结束后,不同GL浓度组在37 ℃下分别用0.5、1.0、2.0 mmol/L浓度的GL刺激24 h.采用细胞计数试剂盒8(CCK-8)法检测5组细胞存活率,检测5组细胞活性氧(ROS)水平,Western blot法检测HO-1、Kelch样ECH相关蛋白1(Keap1)、Nrf2蛋白表达水平.将24只SD大鼠分为正常组、模型组和GL干预组,每组8只;后两组大鼠给予含5%右旋葡聚糖硫酸酯钠盐的饮用水构建UC模型.观察并记录3组大鼠的疾病活动指数(DAI)、组织损伤指数(TDI);实验结束后处死各组大鼠,测量结肠长度,检测结肠组织的超氧化物歧化酶(SOD)、丙二醛(MDA)水平;采用Western blot法检测结肠组织HO-1、Keap1、Nrf2蛋白表达水平.结果 细胞实验结果显示,与模型组比较,低、中、高GL浓度组细胞存活率均提高(均P<0.05),细胞内ROS水平明显下降(P<0.05),HO-1蛋白表达水平明显增加(P<0.05),中、高GL浓度组Nrf2蛋白表达水平明显增加(均P<0.05),中、高GL浓度组Keap1蛋白表达水平明显下降(均P<0.05).动物实验结果显示,与模型组比较,GL干预后大鼠的DAI和TDI均明显下降(均P<0.05),结肠长度更长(P<0.05),结肠组织SOD水平明显升高(P<0.05),MDA水平明显下降(P<0.05),Nrf2和HO-1蛋白表达水平均明显升高(均P<0.05),Keap1蛋白表达水平明显下降(P<0.05).结论 GL可能通过增强Nrf2/HO-1信号通路,抑制氧化应激诱导的UC损伤,从而发挥治疗作用.
Glycyrrhizin suppresses oxidative stress injury in ulcerative colitis through Nrf2/HO-1 signaling pathway
Objective To investigate the effect of glycyrrhizin(GL)on oxidative stress in ulcerative colitis(UC)and its relation with nuclear factor erythroid-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods HT-29 cells were randomly divided into normal group,model group and low,medium and high GL concentration group.The oxidative stress model was induced in HT-29 cells by adding 0.8 mmol/L H2O2 in culture media,and the model cells were treated with 0.5,1.0,and 2.0 mmol/L concentration of GL for 24 h.The cell viability was detected by cell counting kit-8 method,the level of reactive oxygen species(ROS)was detected,and the protein expressions of HO-1,Kelch-like ECH-associated protein 1(Keap1),and Nrf2 were detected by Western blot.Twenty-four SD rats were divided into normal,model and GL intervention groups,with 8 rats in each group.The UC was induced by adding 5%dextran sulfate sodium salt in drinking water in model and GL intervention groups.The disease activity index(DAI)and tissue damage index(TDI)of rats were observed;rats were sacrificed at the end of the experiment,the length of colon was measured,and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in colon tissues were detected;and the expressions of HO-1,Keap1 and Nrf2 in colon tissues were detected by Western blot.Results Compared with the model cell group,the cell survival rate was increased in the low,medium and high GL concentration groups(all P<0.05),the intracellular ROS level was decreased(P<0.05),the expression of HO-1 and Nrf2 was increased in medium and high GL concentration groups(all P<0.05);while the expression of Keap1 in the medium and high GL concentration groups decreased(both P<0.05).Compared with the model rats,DAI and TDI decreased(both P<0.05),colon length was longer(P<0.05),SOD level in colon tissue increased(P<0.05),MDA level decreased(P<0.05),Nrf2 and HO-1 expression significantly increased(both P<0.05),and Keap1 protein expression decreased in the GL intervention rats(P<0.05).Conclusion GL may suppress oxidative stress-induced injury by modulating the Nrf2/HO-1 signaling pathway,to exert therapeutic effects on ulcerative colitis.

GlycyrrhizinUlcerative colitisAntioxidant stressNuclear factor erythroid-related factor 2/heme oxy-genase-1 signaling pathway

刘勇攀、郑东元、徐勤科

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310005 杭州,浙江中医药大学附属第二医院消化内科

浙江中医药大学第二临床医学院

甘草酸苷 溃疡性结肠炎 氧化应激 核因子红系相关因子2/血红素加氧酶1信号通路

2024

浙江医学
浙江省医学会

浙江医学

CSTPCD
影响因子:0.428
ISSN:1006-2785
年,卷(期):2024.46(23)