北京中医药大学学报2024，Vol.47Issue(11)：1541-1549,9.DOI:10.3969/j.issn.1006-2157.2024.11.009
基于NLRP3炎症小体探讨降糖3号方缓解糖尿病小鼠炎症反应的分子机制
The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome
摘要
Abstract
Objective This study aimed to observe the effect of Jiang Tang San Hao Formula(JTSHF)on systemic and intestinal inflammation,as well as on the NLRP3 inflammasome in type 2 diabetic mice(T2DM),and to elucidate its anti-diabetic molecular mechanisms.Methods Four-week-old male C57BL/6 N mice were used to establish the T2DM model using a high-fat diet combined with streptozotocin injection.The diabetic mice were randomly divided into the model,metformin,and JTSHF groups.A control group was also set to provide baseline comparisons.Each group of mice was orally administered with the corresponding medication daily.The metformin group was orally administered with 0.20 g/kg metformin,the JTSHF group was orally administered with 4.26 g/kg JTSHF,and the control group and model group were orally administered with an equal amount of sterile water continuously for 8 weeks.After an 8-week drug intervention via gavage,the lipopolysaccharide(LPS),tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6)serum and colon levels were quantified using an enzyme-linked immunosorbent assay(ELISA).The pathological morphology of the colon was observed using hematoxylin and eosin staining.NOD-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,zonula occludens-1(ZO-1),occludin,and G-protein coupled receptor 43(GPR43)protein expression in the colon were assessed using immunohistochemistry.The mRNA expression levels of NLRP3,ASC,caspase-1,ZO-1,Occludin,and GPR43 in the colon were detected using Real-time PCR.Results The ELISA data revealed significant differences in inflammatory markers among the groups.Compared with the model group,the JTSHF group exhibited notably reduced LPS,TNF-α,IL-1β,and IL-6 levels(P<0.05).Moreover,compared with the model group,JTSHF treatment upregulated ZO-1,occludin,and GPR43 protein and mRNA expression in the colon and downregulated NLRP3,ASC,and Caspase-1 protein and mRNA expression(P<0.05).Conclusion The inflammatory reaction of T2DM mice is apparent.JTSHF effectively alleviates the systemic and intestinal inflammatory response of T2DM mice by inhibiting the NLRP3 inflammasome and repairing the intestinal mucosal barrier,highlighting the potential molecular mechanisms of the anti-diabetes effects of JTSHF.关键词
2型糖尿病/降糖3号方/炎症反应/NLRP3炎症小体/肠黏膜屏障/小鼠Key words
type 2 diabetes/Jiang Tang San Hao Formula/inflammatory reaction/NLPR3 inflammasome/intestinal mucosal barrier/mice分类
医药卫生引用本文复制引用
赵祎,高思华,赵丹丹,李润琪,徐冰蕊,叶紫梦玮,莫芳芳,田甜,董广通,马如风,杨晓达..基于NLRP3炎症小体探讨降糖3号方缓解糖尿病小鼠炎症反应的分子机制[J].北京中医药大学学报,2024,47(11):1541-1549,9.基金项目
国家自然科学基金项目(No.82174329) （No.82174329）
北京中医药大学基本科研业务费揭榜挂帅项目(No.2023-JYB-JBZD-010) （No.2023-JYB-JBZD-010）
国家中医药领军人才支撑计划-岐黄学者项目(No.1040063321005) National Natural Science Foundation of China(No.82174329) （No.1040063321005）
