黄连肉桂对自发性2型糖尿病小鼠胆汁酸代谢、肠上皮Occludin蛋白表达及小肠形态结构改变的影响

Effects of Rhizoma Coptidis and Cortex Cinnamomi on bile acid metabolism,Occludin expression in intestinal epithelium and morphology and structure changes of small intestinal in spontaneous type 2 diabetic mice

目的观察黄连肉桂通过对自发性2型糖尿病(diabetes mouse,db/db)小鼠胆汁酸代谢、肠上皮紧密连接蛋白(Occludin)表达及小肠形态结构改变的降糖机制。方法以6只db/m小鼠为空白组,30只db/db小鼠随机分成5组,每组6只;实验组分别用二甲双胍、黄连、肉桂及黄连肉桂进行干预,对照组给予等量的生理盐水,在8周测量每组小鼠的血糖同时测量小鼠空腹胰岛素;利用液相色谱法检测小鼠粪便胆汁酸的代谢含量、蛋白免疫印迹法检测回肠Occludin蛋白的表达、电镜扫描小鼠小肠形态学的改变。结果黄连肉桂可以有效改善db/db小鼠的高血糖状态、降低小鼠血糖,与模型组相比差异有统计学意义(P<0.05),同时可以增加db/db小鼠胆汁酸中胆酸(cholic acid,CA)、鹅去氧胆酸(chenodeoxy cholic acid,CDCA)分泌,减少熊去氧胆酸(Ursodeoxy cholic acid,UDCA)分泌,与模型组相比差异有统计学意义(P<0.05)。黄连肉桂能够增加小鼠回肠Occludin蛋白的表达,与模型组相比差异有统计学意义(P<0.05);还能够改善db/db小鼠肠道超微状态、增强肠道屏障作用、降低其通透性。结论黄连肉桂可以改善db/db小鼠高血糖状态,其机制可能与其可以调节胆汁酸分泌和增加肠Occludin蛋白表达,增强肠道屏障作用、降低其通透性有关。

Objective To observe the hypoglycemic mechanism of Rhizoma Coptidis and Cortex Cinnamomi by inhibiting bile acid metabolism,intestinal epithelial tight junction protein(Occludin)expression and morphological and structure changes of small intestine in spontaneous type 2 diabetic mice(db/db)mice.Methods 6 db/m mice were used as the blank group,30 db/db mice were randomly divided into 5 groups,with 6 mice in each group.The experimental groups were intervened with metformin,Rhizoma Coptidis,Cortex Cinnamomi,Rhizoma Coptidis and Cortex Cinnamomi respectively,the control group was given the same amount of normal saline.Blood glucose and fasting insulin were measured in each group at 8 weeks.The metabolic content of bile acid in the feces of mice was determined by liquid chromatography.Western blot(WB)was used to detect the protein expression of Occludin in ileum.Morphological changes of small intestine in mice by scanning electron microscopy.Results Rhizoma Coptidis and Cortex Cinnamomi can effectively improve the hyperglycemia state of db/db mice and reduce the blood glucose of mice.Compared with the model group(P<0.05),the secretion of cholic acid(CA)and chenodeoxy cholic acid(CDCA)of bile acid in db/db mice were increased,and the secretion of ursodeoxy cholic acid(UDCA)was decreased.Compared with the model group(P<0.05),the protein expression of Occludin in ileum of mice was increased(P<0.05),the intestinal ultramicrostate of db/db mice was improved,the intestinal barrier function was enhanced,and its permeability was reduced.Conclusion Rhizoma Coptidis and Cortex Cinnamomi can improve the hyperglycemia state of db/db mice,and its mechanism may be related to regulating the secretion of bile acid,increasing the protein expression of Occludin in intestinal so as to enhancing the intestinal barrier,and reducing its permeability.