【摘要】 目的探讨2型糖尿病大鼠肝胆汁酸代谢的变化。方法 35只SD雄性大鼠随机分为对照组15只和糖尿病组20只,分别喂以标准饲料和高脂饲料,8 w后通过口服糖耐量实验,胰岛素敏感指数(ISI),证实是否产生胰岛素抵抗。出现胰岛素抵抗的大鼠注射小剂量链脲佐菌素(STZ)以诱导2型糖尿病。成膜大鼠继续用高脂饲料喂养4 w,每组随机取10只大鼠,总胆管插管收集胆汁,股动脉采血,并留取部分肝组织。检测血生化指标,胆汁中胆汁酸、胆固醇和磷脂的浓度,RT-PCR检测胆汁酸代谢有关基因LXRα、CYP7A1、ABCG5和ABCG8 mRNA表达。结果与对照组相比,糖尿病组大鼠空腹血糖、甘油三酯、胆固醇、胆汁酸以及胰岛素敏感指数明显升高(P<0.01),体重明显增高(P<0.05);与对照组相比较,糖尿病组大鼠胆汁中胆汁酸和胆固醇含量均有明显增加(P<0.01),磷脂含量也有一定增加(P<0.05),但胆汁酸和磷脂浓度总和与胆固醇浓度比值下降(P<0.01);糖尿病组LXRα、CYP7A1、ABCG5和ABCG8 mRNA水平均明显高于对照组(P<0.05或P<0.01)。结论 2型糖尿病状态下,肝胆汁酸合成增加,由肝细胞进入胆汁中的胆汁酸和胆固醇均增加,胆结石形成的可能性增大。更多还原

【Abstract】 Objective To investigate metabolic changes of bile acid of type 2 diabetes(T2DM).Methods 35 male SD rats were randomly divided into control(Con group) and diabetes mellitus groups(DM group),with 15 and 20 respectively.Rats in Con group and DM group were fed with normal diet and high-fat diet,respectively.8 weeks later,OGTT and ISI test were performed to identify insulin resistance(IR).The IR rats received intraperitoneal injection of low-dose streptozotocin to induce T2DM.After giving high-fat diet further 4 more weeks,10 rats of each group were sacrificed,and bile,artery blood and liver sample were taken for further analysis.Serum biochemical indexes and concentrations of bile acid,cholesterol and phospholipid in bile were detected.The mRNA level of genes involved in bile acid metabolism was evaluated by RT-PCR.Results Compared with the Con group,the serum levels of fasting glucose,triglyceride,cholesterol,bile acid and insulin sensitivity index of DM group were significantly elevated(P<0.01),body weight of DM group increased significantly(P<0.05).The concentrations of bile acid and cholesterol in diabetic rats biles were significantly increased(P<0.01),and the concentrations of phospholipid in diabetic rats bile were also increased to some extent(P<0.05),but the(bile acid + phospholipid)/cholesterol ratio decreased(P<0.01).The mRNA of LXRα,CYP7A1,ABCG5 and ABCG8 of DM group were significantly higher than that of Con group(P<0.05,P<0.01).Conclusions In T2DM state,hepatic bile acid synthesis is increased,and bile acid and cholesterol in bile are increased,and the possibility of cholesterol gallstone formation is increased.更多还原