健脾清化方调控RasGRP1/P38 MAPK通路影响肠道通透性对高脂饮食诱导肥胖小鼠胰岛素抵抗的改善作用  

Effects of Jianpi Qinghua Recipe on improving insulin resistance in DIO mice by regulating RasGRP1/P38 MAPK pathway to affect intestinal permeability

作　　者：刘亚华 韩煦 金燊懿 蔡梦洁 陈清光[1] 陆灏[1] LIU Ya-hua;HAN Xu;JIN Shen-yi;CAI Meng-jie;CHEN Qing-guang;LU Hao(Department of Endocrinology,Diabetes Institute,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院内分泌科,糖尿病研究所,上海201203

出　　处：《中华中医药杂志》2021年第5期2647-2651,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81874434,No.81774235,No.82074381);上海市中医临床重点实验室(No.20DZ2272200);上海市科委科研计划项目(No.17401970100,No.14401930600);中医糖尿病专科联盟建设[No.ZY(2018-2020)-FWTX-4011]。

摘　　要：目的:探讨健脾清化方调控高脂饮食诱导肥胖(DIO)、胰岛素抵抗(IR)小鼠RasGRP1/P38 MAPK通路,影响肠道通透性,对改善全身胰岛素抵抗的作用。方法:采用DIO、IR小鼠模型,随机分为正常组、模型组、健脾清化方组、二甲双胍组,连续灌胃给药6周,腹腔糖耐量、腹腔胰岛素耐量实验观察DIO小鼠血糖、胰岛素分泌水平,并计算曲线下面积(AUC);免疫荧光染色法观察小鼠肠道组织RasGRP1的定位及表达;Western blot法检测小鼠肠道组织RasGRP1、p-P38 MAPK/P38 MAPK、紧密连接蛋白(ZO-1、Occludin)的蛋白表达水平。结果:与模型组比较,健脾清化方组显著下调IR小鼠的体质量、血糖水平和AUC(P<0.01),下调肠道组织RasGRP1蛋白的表达及p-P38 MAPK/P38 MAPK(P<0.01);上调ZO-1、Occludin蛋白水平(P<0.05,P<0.01)。结论:健脾清化方缓解IR,其作用机制可能与肠道组织中RasGRP1/P38 MAPK通路影响肠道通透性有关。Objective:To explore the effects of Jianpi Qinghua Recipe on improving systemic insulin(IR)by regulating RasGRP1/P38 MAPK pathway in the intestine of high-fat diet induced obesity(DIO)mice and effecting intestinal permeability.Methods:The obese and IR mice induced by high-fat diet were randomly divided into normal group,model group,Jianpi Qinghua group,metformin group.After 6 weeks continuous intragastric administration,intraperitoneal glucose tolerance(IPGTT)and intraperitoneal insulin tolerance(IPITT)were conducted to measure the level of blood glucose and insulin of DIO mice,and the area under the curve(AUC)was calculated;The immunofluorescence staining(IF)was applied to observe the localization and expression of RasGRP1 in intestinal tissue;Western blot was used to detect the protein expression of RasGRP1,p-P38 MAPK/P38 MAPK,tight junction protein(ZO-1,Occludin)in intestinal tissues.Results:Compared with the model group,Jianpi Qinghua group reduced the body weight,blood glucose level and the AUC of obese and IR mice significantly(P<0.01),weakened the expression of RasGRP1 and the p-P38 MAPK/P38 MAPK in intestinal tissues(P<0.01)and relieved the protein levels of ZO-1 and Occludin(P<0.05,P<0.01).Conclusion:Jianpi Qinghua Recipe could ameliorate IR,which might be related to the effect of RasGRP1/P38 MAPK pathway on intestinal permeability.

关 键 词：健脾清化方 RasGRP1 P38 MAPK 肠道通透性 胰岛素抵抗 高脂饮食诱导肥胖 

分 类 号：R285.5[医药卫生—中药学]