乳酸菌混合物通过激活胆汁酸-TGR5-GLP-1轴改善糖尿病肥胖小鼠血糖及肠道屏障功能实验研究OA

Objective:To investigate the effects of lactic acid bacteria mixture on blood glucose and intestinal barrier function in diabetic obese mice based on the bile acid-G protein-coupled bile acid receptor 5(TGR5)-glucagon-like peptide 1(GLP-1)axis.Methods:The C57 BL/6J mice were randomly divided into control group(12 mice),mod-el group(14 mice),metformin positive drug group(14 mice),and lactic acid bacteria mixture group(14 mice).The diabetes-obesity mouse model was constructed by feeding with high-fat diet and intraperitoneal injection of streptozo-tocin.The body weight,fasting blood glucose,serum insulin and total bile acid levels of each group were detected;RT-qPCR and Western blot were used to detect the expression of TGR5 and GLP-1 mRNA and protein in the colon tissue;immunohistochemical staining was used to detect the expression of GLP-1 receptor(GLP-1R)protein in the pancreatic tissue;HE staining was used to detect the pathological changes of the colon tissue;Western blot was used to detect the expression of ZO-1,Claudin-1 and Occludin proteins in the colon tissue.Results:Compared with the con-trol group,the body weight and fasting blood glucose of the model group increased(all P<0.05),while the levels of insulin,total bile acid,TGR5,GLP-1,GLP-1R,ZO-1,Claudin-1,and Occludin decreased(all P<0.05),and the colon tissue showed edema,and there was a large infiltration of inflammatory cells.Compared with the model group,the positive drug group had decreased body weight and fasting blood glucose(all P<0.05),while the levels of total bile acid,TGR5,GLP-1,ZO-1,Claudin-1,and Occludin increased(all P<0.05),and the edema and inflammatory cell in-filtration in the colon tissue were alleviated;the fasting blood glucose of the lactic acid bacteria mixture group de-creased(P<0.05),and the levels of total bile acid,insulin,TGR5,GLP-1,GLP-1R,ZO-1,Claudin-1,and Occludin increased(all P<0.05),and the edema and inflammatory cell infiltration in the colon tissue were alleviated.Com-pared with the positive drug group,the mice in the lactic acid bacteria mixture group had decreased fasting blood glu-cose(P<0.05),and the levels of total bile acid,TGR5,GLP-1,ZO-1,Claudin-1,and Occludin increased(all P<0.05),and had further reduced colonic tissue edema and infiltration of inflammatory cells.Conclusion:The lactic acid bacteria mixture reduces blood glucose and improves the intestinal barrier function of diabetic obese mice by activa-ting the bile acid-TGR5-GLP-1 axis.