Roux-en-Y胃旁路术对GK大鼠骨骼肌组织胰岛素抵抗影响的机制研究  

Mechanism of Roux-en-Y Gastric Bypass Surgery in Improving Skeletal Muscles Insulin Resistance of GK Rats

作　　者：王勇[1] 白洁[1] 匡立润[1] 刘金钢[1] 

机构地区：[1]中国医科大学附属盛京医院普通外科,辽宁沈阳110004

出　　处：《中国普外基础与临床杂志》2014年第2期162-167,共6页Chinese Journal of Bases and Clinics In General Surgery

基　　金：国家自然科学基金资助项目(编号:81000158)~~

摘　　要：目的探讨Roux-en-Y胃旁路术(RYGB)改善2型糖尿病大鼠(Goto-Kakizaki大鼠,GK大鼠)骨骼肌胰岛素抵抗的可能机制。方法 30只GK大鼠随机分为GK-RYGB组、GK-假手术组、GK-对照组,另取10只Wistar大鼠作为正常对照组。术后28 d时处死实验动物。ELISA法检测血浆ghrelin浓度,免疫印迹法检测骨骼肌组织的磷酸化(p)-/总(t)-PI3Kp85α、p-/t-Akt/PKB及细胞膜(m)-/t-GLUT4蛋白的相对表达量,实时荧光定量PCR法检测骨骼肌组织中PI3Kp85α、Akt/PKB及GLUT4 mRNA的表达。结果①血浆ghrelin浓度在正常对照组明显高于GK-对照组(P<0.01)和GK-假手术组(P<0.01);GK-RYGB组也明显高于GK-对照组(P<0.01)及GK-假手术组(P<0.01),但与正常对照组相比差异无统计学意义(P>0.05)。②p-/t-PI3Kp85α、p-/t-Akt/PKB及m-/t-GLUT4蛋白相对表达量在正常对照组均较GK-对照组(分别P<0.01、P<0.05、P<0.01)和GK-假手术组(分别P<0.01、P<0.05、P<0.01)明显上升;GK-RYGB组亦较GK-对照组(分别P<0.01、P<0.05、P<0.01)和GK-假手术组(分别P<0.01、P<0.05、P<0.01)均分别明显上升。③骨骼肌组织中PI3Kp85α、Akt/PKB及GLUT4 mRNA的表达在正常对照组均较GK-对照组(分别P<0.01、P<0.05、P<0.05)和GK-假手术组(分别P<0.01、P<0.05、P<0.05)明显上升;GK-RYGB组较GK-对照组(分别P<0.01、P<0.05、P<0.05)和GK-假手术组(分别P<0.01、P<0.05、P<0.05)也均分别明显上升。结论①RYGB术后GK大鼠血浆ghrelin水平显著升高。②RYGB术能够上调GK大鼠骨骼肌组织中PI3Kp85α、Akt/PKB mRNA和磷酸化蛋白的表达,并上调GLUT4的转录和翻译,促使更多的GLUT4在细胞膜表达,增加骨骼肌组织对葡萄糖的摄取,从而改善骨骼肌组织的胰岛素抵抗。Objective To investigate the possible mechanism of the improvement of type 2 diabetes mellitus with insulin resistance of skeletal muscles after Roux-en-Y gastric bypass surgery （RYGB）. Methods Thirty GK rats were randomly divided into GK-RYGB group, sham operation group （GK-SO group）, and control group （GK-control group） ; in addition, 10 Wistar rats served as normal control group. On day 28, the animals were sacrificed. The ghrelin concen- tration and PI3Kp85ct, Akt/PKB, and GLUT4 levels were measured by ELISA, Western blot, and real-time PCR me- thods, respectively. Results @ Compared with the GK-SO group and GK-control group, the plasma ghrelin levels were significantly increased in the normal control group （P〈 0. 0 l） and GK-RYGB group （P〈 0. 01）. ~）Compared with the GK-SO group and GK-control group, p-/t-PI3Kp85ct, p-A-Akt/PKB, and re-/t-GLUT4 proteins were significantly incre-ased in the normal control group （P〈0. 01, P〈0. 05, and P〈0. 01, respectively） and GK-RYGB group （P〈0.01, P〈 0.05, and P〈0. 01, respectively）. （~）Compared with the GK-SO group and GK-control group, PI3Kp85ct, Akt, and GLUT4 mRNA were significantly increased in the normal control group （P〈0. 01, P〈0. 05, and P〈0. 05, respectively） and GK-RYGB group （P〈0. 01, P〈0.05, and P〈0.05, respectively）. Conclusion RYGB could elevate the ghrelin level obviously and upregulate PI3Kp85ct, Akt/PKB, and GLUT4 levels and thus improve the insulin resistance of skeletal muscles of rats with T2DM.

关 键 词：骨骼肌胰岛素抵抗 ROUX-EN-Y胃旁路术 GHRELIN P13K Akt PKB通路 

分 类 号：R656.6[医药卫生—外科学] R587.1[医药卫生—临床医学]