雷公藤多苷通过Nur77-Traf2-P62信号通路治疗溃疡性结肠炎的机制研究  

Mechanistic study of tripterygium glycosides in the treatment of ulcerative colitis through the Nur77-Traf2-P62 signaling pathway

作　　者：钟继红 刘勇攀 陈丹丹 黄秋薇 张馨瑞 徐勤科 叶露 ZHONG Jihong;LIU Yongpan;CHEN Dandan;HUANG Qiuwei;ZHANG Xinrui;XU Qinke;YE Lu(Department of Gastroenterology,the Second Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310005,Zhejiang,China;the Second Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China)

机构地区：[1]浙江中医药大学附属第二医院消化内科,浙江省肠肝同治中医重点实验室,浙江杭州310005 [2]浙江中医药大学第二临床医学院,浙江杭州310053

出　　处：《中国现代医生》2024年第11期58-62,共5页China Modern Doctor

基　　金：浙江省自然科学基金项目(Y21H290016)。

摘　　要：目的研究雷公藤多苷(tripterygium glycosides,TG)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)小鼠结肠黏膜损伤的影响及调控机制。方法将40只小鼠采用随机数字表法分为正常组,模型组,雷公藤多苷低、中、高剂量组(给药浓度分别为9.00、27.03、81.09mg/kg)。除正常组外,其余组小鼠均饮用5%DSS诱导UC模型。造模后,模型组小鼠予生理盐水灌胃,其余处理组小鼠予相应剂量的TG灌胃。比较各组小鼠的质量、疾病活动指数(disease activity index,DAI)、结肠病理组织学损伤情况。使用肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)试剂盒检测TNF-α、MDA、SOD水平差异。Western blot法检测结肠中Nur77、TNF受体关联因子2(tumor necrosis factor receptor-associated factor 2,Traf2)、核孔蛋白62(nucleoporin 62,P62)、自噬蛋白微管相关蛋白1轻链3(autophagy protein-microtubule associated protein1 light chain 3,LC3)分子表达。结果与空白组相比,模型组小鼠的体质量、结肠长度、SOD、Nur77、Traf2、LC3Ⅱ/LC3Ⅰ水平降低(P<0.05),DAI、结肠病理评分、TNF-α、MDA、P62水平升高(P<0.05)。与模型组相比,雷公藤多苷低、中、高剂量组小鼠体质量、结肠长度、SOD、Nur77、Traf2、LC3Ⅱ/LC3Ⅰ表达增长(P<0.05),DAI、TNF-α、MDA、P62水平均降低(P<0.05)。雷公藤多苷中、高剂量组小鼠病理评分降低(P<0.05)。结论TG能够通过Nur77-Traf2-P62信号通路治疗UC。Objective To investigated the effect of tripterygium glycosides(TG)on dextran sodium sulfate(DSS)-induced colonic mucosal damage in ulcerative colitis(UC)mice and its regulatory mechanism.Methods Forty C57BL/6J mice were randomly divided into a normal group,a model group,and a tretinoin low,medium,and high dose group(administered at concentrations of 9.00mg/kg,27.03mg/kg,and 81.09mg/kg,respectively).The mice in the normal group were free to drink distilled water,and the rest of the mice drank 5%DSS to induce UC modeling.After modeling,mice in the model group were given 0.4ml of saline by gavage daily,and the rest of the mice in the treatment group were given the corresponding dose of TG for gavage intervention.The mass and disease activity index of the mice in each group were compared,and the pathological and histological damage of the colon was observed.Tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)levels were measured using the corresponding kits.Western blot Detection of Nur77,tumor necrosis factor receptor-associated factor 2(Traf2),nucleoporin 62(P62),autophagy protein-microtubule associated protein1 light chain 3(LC3)molecular expression.Results Compared with the blank group,the body weight,colon length,SOD,Nur77,Traf2,and LC3II/LC3Ⅰlevels of mice in the model group were significantly decreased(P<0.05),and the DAI level,colon pathology score,TNF-α,MDA level,and P62 of the mice were significantly increased(P<0.05).Compared with mice in the UC model group,mice in the low,medium and high dose groups of tretinoin polyphenols showed significant increases in body weight,colon length,SOD,Nur77,Traf2,LC3II/LC3Ⅰlevels(P<0.05),and mice with DAI scores,TNF-α,MDA levels in the colon,and P62 levels were significantly decreased(P<0.05).Mice in the medium and high dose groups of tretinoin polyphenols pathological scores were significantly reduced(P<0.05).Conclusion TG is able to treat ulcerative colitis through Nur77-Traf2-P62 signaling pathway.

关 键 词：雷公藤多苷 溃疡性结肠炎 Nur77-Traf2-P62信号通路 自噬 

分 类 号：R574[医药卫生—消化系统]