肥胖2型糖尿病患者与大鼠胃旁路术后血清总胆汁酸水平的变化

Effects of gastric bypass surgery on serum total bile acid in obese diabetic patients and rats

目的:观察胃旁路术对肥胖2型糖尿病患者及肥胖2型糖尿病模型大鼠血清总胆汁酸水平的影响,并探讨其分子机制。方法:收集并分析2011年6月~2016年6月暨南大学附属第一医院肥胖2型糖尿病患者共87例术后血糖恢复情况及血清总胆汁酸水平变化数据。动物实验选用SD大鼠,高脂喂养联合腹腔注射低剂量链脲佐菌素的方法制作肥胖2型糖尿病模型,分为正常对照(普通饲料喂养非手术)组、胃旁路手术组及假手术组,检测手术前后大鼠血糖及血清总胆汁酸水平,HE染色观察大鼠胰腺组织病理变化,ELISA方法检测大鼠肝组织胆固醇7α-羟化酶(CYP7A1)含量,real-time PCR和Western blot分别检测各组大鼠肝组织CYP7A1和小分子异源二聚体伴侣(SHP)mRNA和蛋白水平。结果:肥胖2型糖尿病患者及模型大鼠胃旁路术后空腹血糖降低,血清总胆汁酸水平升高,肝组织合成胆汁酸经典途径的限速酶CYP7A1含量降低,CYP7A1 mRNA和蛋白表达量均减少,肝组织胆汁酸合成的负性调节因子SHP mRNA和蛋白表达量均增加,与假手术组比较差异显著(P<0.05)。结论:胃旁路手术后肥胖2型糖尿病患者及模型动物血清总胆汁酸水平升高,且该变化并非因经典途径合成胆汁酸增多。

AIM：To observe the effects of gastric bypass surgery on the levels of serum total bile acid in the obese diabetic patients and rats .METHODS： Anthropometric data of obese diabetic patients with gastric bypass surgery from June 2011 to June 2016 were collected in the First Affiliated Hospital of Jinan University .Obese diabetic animal mo-del was established in SD rats by high-fat diet feeding combined with intraperitoneal injection of low-dose streptozocin .Gas-tric bypass surgery or sham operation was performed on the rats with successful modeling .The levels of serum total bile acid were measured by a Hitachi automatic biochemistry analyzer , and the content of hepatic cholesterol 7α-hydroxylase （CYP7A1） was detected by ELISA.The expression of hepatic CYP7A1 and small heterodimer partner （SHP） at mRNA and protein levels was determined by real-time PCR and Western blot, respectively.RESULTS：The serum levels of total bile acid were significantly increased in postoperative obese diabetic patients and rats as compared with control groups .Gas-tric bypass surgery inhibited rat hepatic CYP 7A1 content, mRNA level and protein level , but stimulated hepatic SHP ex-pression.CONCLUSION：Total serum bile acid increases in both patients and rats after gastric bypass surgery by non -typical bile acid synthesis pathway .