消胆胺联合阿嗪米特对糖尿病小鼠胆汁酸代谢的影响  

Effects of Cholestyramine Combined with Azintamide on Bile Acid Metabolism in Diabetic Mice

作　　者：梁业飞[1] 周有望 陶文[3] 

机构地区：[1]广西壮族自治区钦州市第一人民医院药剂科,钦州535001 [2]广西壮族自治区百色市人民医院药学部,百色533000 [3]广西中医药大学第一附属医院药学部,南宁530023

出　　处：《医药导报》2015年第2期146-150,共5页Herald of Medicine

摘　　要：目的探讨消胆胺联合阿嗪米特对糖尿病小鼠胆汁酸代谢的影响。方法构建糖尿病小鼠模型,将实验小鼠随机分为4组,每组20只。正常对照组以普通饲料饲养;模型对照组以高脂高糖饲料饲养;消胆胺组在高脂高糖饲料中添加消胆胺饲养;联合治疗组在高脂高糖饲料中添加消胆胺及阿嗪米特饲养。监测空腹血糖,饲养12周后,处死小鼠,胆汁酸检测试剂盒测定大便、肝脏、血液中胆汁酸浓度,逆转录聚合酶链反应(RT-PCR)检测胆汁酸代谢相关基因[核受体法尼醇X受体基因(FXR)、胆固醇7α羟化酶基因(CYP7A1)、胆固醇27α羟化酶基因(CYP27A1)]的mRNA表达,Western blot检测CYP7A1和CYP27A1的蛋白表达情况。结果消胆胺联合阿嗪米特协同治疗使糖尿病小鼠空腹血糖显著降低(P<0.05),大便、血液、肝脏中胆汁酸浓度显著增加(P<0.05或P<0.01),与胆汁酸代谢相关的FXR基因mRNA表达减少,CYP7A1基因mRNA表达增加,CYP7A1蛋白表达也显著增加,而CYP27A1基因mRNA及蛋白表达无明显差异。结论消胆胺联合阿嗪米特可增强糖尿病小鼠胆汁酸合成,此过程与胆汁酸经典合成途径相关。Objective To investigate the effect of cholestyramine and azintamide therapeutic alliance on bile acid metabolism in diabetic mice. Methods Construction of diabetic mice model , the nfiee were randomly divided into flmr groups： normal control group： with ordinary diet f^eding; model control group： with high fat and sugar diet feeding; cholestyramine group： adding cholestyramine into high fat and sugar diet feeding; combined treatment group： adding cholestyranfine and azintamide into high fat and sugar diet feeding. Monitoring blood glueose, after 12 weeks , the mice were sacrificed. Bile acid test kit measured feces, liver, blood bile acid concentration. RT-PCR detect bile acid metabolism related genes FXR, CYF-/AI, CYP27A1 mRNA expression. Western blot deteet CYP7A1 and CYP27A1 protein expression. Results With cholestyramine and azintamide combined therapy, the blood glucose of diabetic mice signifieantly reduced, feces, blood and liver bile aeid concentration significantly increased, FXR mRNA expression redueed, CYP7A1 mRNA expression increased, CYP7A1 protein expression was also significantly increased, and CYP27A1 mRNA and protein expression was not significantly different. Conclusion Cholestyramine and azintamide combination therapy in diabetic mice can be enhanced bile acid synthesis, this process associated with the classical bile acids synthesis pathway.

关 键 词：消胆胺 阿嗪米特 胆汁酸代谢 小鼠 糖尿病 

分 类 号：R965[医药卫生—药理学] R977.15[医药卫生—药学]