Roux-en-Y胃旁路术改善2型糖尿病大鼠肝脏胰岛素敏感性的机制研究

Mechanisms of amelioration in hepatic insulin sensitivity after Roux-en-Y gastric bypass surgery intype 2 diabetic rats

目的观察Roux—en—Y胃旁路术（Roux—eTl—Ygastricbypass，RYGB）后2型糖尿病大鼠肝脏和外周组织胰岛素敏感性的变化，并探讨其机制。方法采用高脂饮食联合腹腔注射iJ,N量链脲佐菌素建立2型糖尿病大鼠模型，将造模成功的糖尿病大鼠随机分为RYGB手术组和RYGB假手术组，每组10只。采用清醒状态扩展高胰岛素一正血糖钳夹术评估肝脏和外周组织胰岛素敏感性，油红O定性、比色法定量检测肝脏组织中甘油三酯含量．比色法测定肝脏组织丙二醛和超氧化物歧化酶活性，Westernblot方法检测大鼠肝脏组织中蛋白激酶R样内质网激酶和磷酸化蛋白激酶R样内质网激酶的蛋白表达。结果与RYGB假手术组大鼠比较．RYGB手术组术后2周大鼠肝脏敏感性指数增加近50％（P=0．003），肝脏组织中甘油三酯含量降低30％（P=0．000），肝脏组织中丙二醛／超氧化物歧化酶比值下降，磷酸化蛋白激酶R样内质网激酶蛋白表达显著减少（P=0．000）。结论RYGB手术减少肝内脂肪蓄积，降低肝脏脂肪毒性．进而减轻组织氧化应激损伤，下调内质网应激．提高肝脏组织对胰岛素的敏感性．降低血糖。

Objective To investigate the effects of RYGB on hepatic and peripheral insulin sensitivity in type 2 diabetes rats and the mechanisms. Methods Sprague-Dawley rats were divided into 2 groups： diabetic RYGB group （n = 10） and diabetic sham RYGB group （n = 10 ）. The hyperinsulinemic- euglycemic clamp with tracer infusion was completed at 2 weeks postoperatively to assess insulin sensitivity. The lipid content in liver tissue was examined. Malondialdehyde （MDA） and superoxide dismutase （SOD） activities in the liver were measured. The protein expressions of PERK and p-PERK in livers were also detected by Western blot. Results RYGB significantly improved hepatic insulin sensitivity index and decreased hepatic triglyceride concentration （ P 〈 0. 05 ）, without an improvement in peripheral insulin sensitivity, The ratio of MDA to SOD and the protein expression of p-PERK in the livers were lower in the RYGB group than in the sham RYGB group. Conclusions The increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle tissue. The amelioration of hepatic tissue lipotoxicity after RYGB decreased the degrees of oxidative stress and endoplasmic reticulum stress, which may contribute to the improved hepatic insulin sensitivity.