基于“脾为本虚”理论探讨左归复方对2型糖尿病小鼠肠道炎症及黏膜屏障的影响  

Study on effect of Zuogui compound on intestinal inflammation and mucosal barrier in type 2 diabetic mice based on theory of"spleen-based virtual"

作　　者：向琴[1] 蒋宛瑾 喻嵘[1] 邹晓玲[1,2] 吴勇军[1] 刘秀[1] 刘子毓[1] XIANG Qin;JIANG Wan-Jin;YU Rong;ZOU Xiao-Ling;WU Yong-Jun;LIU Xiu;LIU Zi-Yu(Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学第一附属医院,长沙410208

出　　处：《中国免疫学杂志》2020年第6期667-671,676,共6页Chinese Journal of Immunology

基　　金：国家重点研发计划项目(2018YFC17044301,2018YFC1704402);国家自然科学基金项目(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(16C1235,18A220)、湖南中医药大学校级科研基金项目(2017-1)、湖南省研究生科研创新项目(CX2018B483、CX2018B467);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)。

摘　　要：目的:探讨2型糖尿病(T2DM)“脾为本虚”的理论机制及左归复方对T2DM肠道炎症及黏膜屏障的影响及作用机制。方法:采用2型糖尿病MKR模型鼠,连续给予左归复方4周,ELISA法检测胰岛素、炎症相关因子及内毒素浓度,HE染色观察肠道病理形态,RT-qPCR和Western blot检测肠道TLR4/NF-κB通路和紧密连接蛋白的基因和蛋白表达。结果:左归复方可明显降低MKR鼠血糖水平,改善胰岛素抵抗;左归复方可明显抑制炎症因子(IL-1β、IL-6、TNF-α)分泌,降低血液中内毒素浓度;左归复方还能上调肠道紧密连接蛋白Occludin和ZO-1的表达,下调TLR4/NF-κB信号通路的mRNA和蛋白表达。结论:左归复方可通过减轻肠道慢性低度炎症和恢复肠道屏障功能从而改善MKR鼠胰岛素抵抗。Objective:To investigate the theoretical mechanism of"spleen-based deficiency"in T2DM and the effect and mechanism of Zuogui compound on T2DM intestinal inflammation and mucosal barrier.Methods:MKR mice received gavage of Zuogui compound for 4 weeks.Insulin,inflammation-related factors and endotoxin concentrations were detected by ELISA.Pathological morphology of intestinal tissues was observed by HE staining.Expression of TLR4/NF-κB pathway and tight junction protein genes and proteins were detected by RT-qPCR and Western blot.Results:Zuogui compound could significantly reduce the blood glucose level of MKR mice and improve insulin resistance;Zuogui compound could significantly inhibit the secretion of inflammatory factors(IL-1β,IL-6,TNF-α)and reduce the concentration of endotoxin in blood;Zuogui compound also could up-regulate the expression of the tight junction proteins Occludin and ZO-1 and down-regulate the expression of the TLR4/NF-κB mRNA and proteins.Conclusion:Zuogui compound can improve insulin resistance in MKR rats by reducing low-grade chronic inflammation of the intestine and restoring intestinal barrier function.

关 键 词：左归复方 脾虚 病机 2型糖尿病 炎症 黏膜屏障 

分 类 号：R259[医药卫生—中西医结合]