目的 探讨白虎加人参汤对转基因2型糖尿病MKR小鼠肠道屏障及Toll样受4（TLR4）/核转录因子-κB（NF-κB）炎症通路的影响。方法 32只MKR小鼠高脂饮食喂养4周，随机分为模型组，白虎加人参汤低、高剂量（13.5、54.0 g/kg）组，二甲双胍（200 mg/kg）组，8只同龄FVB/N野生小鼠作为对照组。各组ig给药4周后，测定小鼠空腹血糖（FBG）、口服糖耐量（OGTT）、血清炎性因子白细胞介素-6（IL-6）、IL-1β、肿瘤坏死因子-α（TNF-α）和脂多糖（LPS）水平的变化，苏木精-伊红（HE）染色对结肠组织形态进行观察，实时荧光定量PCR（qRT-PCR）检测结肠组织TLR4、NF-κB、ZO-1、Claudin-1、Occludin mRNA表达变化，Western blotting检测结肠组织ZO-1、Claudin-1、Occludin蛋白表达变化。结果 与模型组比较，给药组小鼠FBG水平显著降低（P<0.01），白虎加人参汤高剂量组和二甲双胍组小鼠血清IL-6、IL-1β、TNF-α、LPS水平明显降低（P<0.05、0.01），TLR4、NF-κB mRNA表达明显下调，结肠上皮黏膜完整性明显改善；白虎加人参汤高剂量组和二甲双胍组小鼠ZO-1、Claudin-1、Occludin mRNA和蛋白表达水平显著升高（P<0.05、0.01）；白虎加人参汤低剂量组小鼠ZO-1、Claudin-1、Occludin mRNA表达升高（P<0.05），但蛋白表达水平无明显差异。结论 白虎加人参汤能降低MKR小鼠血清LPS含量及炎症相关因子水平，并调控TLR4/NF-κB信号通路，通过改善内毒素血症、肠道屏障功能，减轻肠道炎症反应，从而改善胰岛素抵抗，降低血糖水平。

Objective To observe the effect of Baihu and Renshen Decoction on intestinal barrier and TLR4/NF-κB inflammatory signaling pathway in type 2 diabetes MKR mice. Methods A total of 32 MKR mice were randomly divided into model group, low dose Baihu and Renshen Decoction group, high dose Baihu and Renshen Decoction group and metformin group after 4 weeks with the high-fat diet. Another eight FVB/N mice were served as control group. After 4-week intragastric administration, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) in serum were examined. The morphological changes of colon tissue were observed by hematoxylin-eosin (HE) staining. The mRNA expression of TLR4, NF-κB, ZO-1, Claudin-1 and Occludin were measured by qRT-PCR method. The protein expression of ZO-1, Claudin-1 and Occludin in colon were measured by Western blotting. Results Compared with model group, FBG in each administration group were significantly decreased (P<0.01), serum IL-6, IL-1β, TNF-α, LPS and TLR4, NF-κB mRNA expressions were decreased (P<0.05, P<0.01) in high dose Baihu and Renshen Decoction group and metformin group. The mucosal epithelium integrity was improved. The mRNA and protein expression levels of ZO-1, Claudin-1, Occludin were increased (P<0.05, P<0.01) in high dose Baihu and Renshen Decoction group and metformin group; The mRNA expression levels of ZO-1, Claudin-1, Occludin were increased (P<0.05) in low dose Baihu and Renshen Decoction group, while protein expressions showed no statistical difference. Conclusion Baihu and Renshen Decoction can consequently reduce the levels of LPS and pro-inflammatory cytokines in MKR mice, regulate TLR4/NF-κB signaling pathway. It can significantly improve insulin resistance and reduce blood glucose levels by improving endotoxaemia, ameliorating intestinal injury and attenuating inflammation.

R285.5

国家自然科学基金资助项目（81573956）；中医方证研究转化医学湖南省重点实验室资助（2018TP1021）；湖南省自然科学基金项目（2018JJ3394）；湖南省中医药科研计划项目（201931）；湖南省教育厅科学研究项目（16C1235）；湖南省教育厅科学研究项目（18A220）；湖南省研究生科研创新项目（CX2018B483）；湖南中医药大学校级科研基金项目（2017-1）；湖南中医药大学大学生研究性学习和创新性实验计划项目（2017-1）