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目的 探讨和中降浊调糖颗粒(HZJZ颗粒)对2型糖尿病(T2DM)小鼠肠屏障的保护作用及缓解炎症的机制。方法 利用高脂高糖饮食+链脲佐菌素构建T2DM小鼠模型，随机分为对照组、T2DM组、HZJZ颗粒低剂量组(6 g/kg)、HZJZ颗粒高剂量组(12 g/kg)和二甲双胍组(200 mg/kg)。给药5周后，检测小鼠空腹血糖(FBG)和口服葡萄糖耐量(OGTT)，利用ELISA法检测血清和肠道中LPS及炎症因子的水平，采用HE和AB-PAS染色观察小鼠结肠组织结构变化，利用Western Blot和免疫荧光染色检测肠屏障完整性和炎症相关蛋白的表达水平。结果 HZJZ颗粒能显著降低T2DM小鼠FBG并改善糖耐量异常；同时，给药组小鼠结肠组织杯状细胞和隐窝数目增加，肠屏障相关蛋白ZO-1、Occludin和Claudin-1表达增加，结肠组织细胞凋亡受抑制；进一步研究发现HZJZ 颗粒降低T2DM小鼠 LPS、IL-6和TNF-α水平，增加IL-10含量，降低TLR4、NF-κB、NLRP3、ASC、Caspase-1、IL-18和IL-1β蛋白表达。结论 HZJZ颗粒能通过TLR4/NF-κB/NLRP3信号通路抑制T2DM小鼠肠道过度的炎症反应，增强肠道屏障的完整性，从而改善T2DM。
Abstract：Objective To investigate the protective effect of Hezhong Jiangzhuo Tiaotang granule (HZJZ granule) on intestinal barrier and its anti-inflammatory mechanism in type 2 diabetes mellitus (T2DM) mice.Methods High-fat and high-sugar diet combined with streptozotocin was used to establish T2DM mice model.And these mice were randomly divided into control group,T2DM group,low dose group of HZJZ(6 g/kg),high dose group of HZJZ (12 g/kg) and metformin group (200 mg/kg).Fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) were measured after continuous administration for 5 weeks.ELISA method was used to detect the levels of LPS and inflammatory factors in the serum and intestine of mice.The changes of colon tissue structure were observed by Hematoxylin-eosin and Alcian blue/periodic acid-Schiff staining.The expression of proteins related to barrier integrity and inflammation were detected by Western Blot and immunofluorescence.Results HZJZ granule significantly reduced FBG and improved abnormal glucose tolerance in T2DM mice.Simultaneously,the number of goblet cells and crypts in the colon of mice in the treated group,and the expression of intestinal barrier-related proteins ZO-1,Occludin and Claudin-1 also increased.And the apoptosis of colon tissue cells was inhibited.Furthermore,HZJZ granule decreased the levels of LPS,IL-6 and TNF-α,while increasing the content of IL-10,and reduced the expression of TLR4,NF-κB,NLRP3,ASC,Caspase-1,IL-18 and IL-1β proteins.Conclusion HZJZ granule can inhibit excessive intestinal inflammation in T2DM mice through the TLR4/NF-κB/NLRP3 signaling pathway and enhance the integrity of the intestinal barrier,thereby improving T2DM.
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基本信息:
DOI：10.13728/j.1673-6427.2025.04.005
中图分类号:R285.5
引用信息:
[1]郭育坤,庞国明,李鹏辉等.和中降浊调糖颗粒对2型糖尿病小鼠肠屏障和肠道炎症的改善作用研究[J].现代中药研究与实践,2025,39(04):27-34.DOI:10.13728/j.1673-6427.2025.04.005.
基金信息:
河南省中医药科学研究重点课题(2023ZY1028); 河南省科技攻关计划项目(202102310370)