基于肠道炎症反应研究降糖3号方抗糖尿病的作用机制  

Anti-diabetic Mechanism of Jiang Tang San Hao Formula Based on Intestinal Inflammation

作　　者：赵祎 徐冰蕊 叶紫梦玮 莫芳芳 穆倩倩 田甜 杨晓达 高思华 赵丹丹 ZHAO Yi;XU Bingrui;YE Zimengwei;MO Fangfang;MU Qianqian;TIAN Tian;YANG Xiaoda;GAO Sihua;ZHAO Dandan(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100007,China;Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]北京中医药大学中医学院,北京100029 [2]北京中医药大学东直门医院,北京100007 [3]北京大学医学部,北京100191

出　　处：《世界中医药》2024年第8期1085-1091,共7页World Chinese Medicine

基　　金：国家自然科学基金项目(82174329);国家中医药领军人才支撑计划-岐黄学者项目(1040063321005);北京中医药大学基本科研业务费揭榜挂帅项目(2023-JYB-JBZD-010);北京市中医药管理局科技发展基金项目(JJ2018-72&JJ2018-72)。

摘　　要：目的:观察降糖3号方对2型糖尿病小鼠肠道炎症相关指标的影响,揭示其抗糖尿病的作用机制。方法:选取4周龄C57BL/6N雄性小鼠,高脂饲料联合小剂量链脲佐菌素(STZ)注射构建2型糖尿病小鼠模型,采用随机数字表法将成模小鼠分成模型组、二甲双胍组、降糖3号方组,每组8只。选取8只标准饲料喂养的小鼠作为正常组。药物干预8周结束后,应用细胞因子抗体芯片技术检测小鼠结肠组织中多种炎症介质水平,并进行差异表达蛋白筛选、基因本体(GO)蛋白功能、京都基因和基因组百科全书(KEGG)通路分析。蛋白质印迹法检测各组小鼠结肠组织中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体激活与肠道黏膜屏障相关的因子G蛋白偶联受体43(GPR43)、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶(Caspase-1)以及闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)的蛋白表达水平。结果:各组间肠道炎症介质差异明显,与模型组比较,降糖3号方组IL-1β、IL-6等炎症介质表达下降,降糖3号方可上调结肠组织中ZO-1、Occludin、GPR43蛋白表达水平,降低ASC、Caspase-1蛋白表达水平(P<0.05)。结论:2型糖尿病小鼠结肠炎症反应明显,降糖3号方能够有效抑制2型糖尿病小鼠肠道炎症,其作用可能与调控NLRP3炎症小体,进而影响下游炎症介质有关。Objective:To observe the effect of Jiang Tang San Hao Formula(JTSHF) on intestinal inflammation in the mouse model of type 2 diabetic mellitus(T2DM) and reveal the anti-diabetic mechanism of JTSHF.Methods:Four-week-old C57BL/6N male mice were selected for the modeling of T2DM by a high-fat diet combined with injection of low-dose streptozotocin(STZ).The modeled mice were then randomized into a model group,a metformin group,and a JTSHF group,with 8 mice in each group.Eight mice were fed with a standard diet and served as the normal group.All the mice were administrated with corresponding drugs for 8 weeks.The cytokine antibody array kit was used to determine the levels of multiple inflammatory mediators in the colon tissue of mice.The differentially expressed proteins were screened,which was followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment.Western blotting was employed to determine the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3(NLRP3) inflammasome and the expression levels zonula occludens-1(ZO-1),occludin,G protein-coupled receptor 43(GPR43),apoptosis-associated speck-like protein containing a CARD(ASC),and caspase-1 in the colon tissue of mice.Results:The levels of inflammatory mediators in the colon tissue differed significantly between groups.Compared with the model group,the JTSHF group showed lowered levels of interleukin-1β(IL-1β) and IL-6,up-regulated expression of ZO-1,occludin,and GPR43,and down-regulated expression of ASC and caspase-1(P<0.05).Conclusion:Obvious inflammation was observed in the colon tissue of T2DM mice,which was reduced by JTSHF.JTSHF may regulate the NLRP3 inflammasome and its downstream inflammatory mediators to exert the therapeutic effect.

关 键 词：糖尿病 降糖3号方 炎症介质 核苷酸结合寡聚化结构域样受体蛋白3炎症小体 抗体芯片 结肠组织 作用机制 

分 类 号：R285.5[医药卫生—中药学]