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

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28d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）。P13Kp85ct、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P13Kp85a、Akt／PKB及GLUT4mRNA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〈O．01）；GK-RYGB组也明显高于GK．对照组∽〈0．01）及GK．假手术组（尸〈0．01），但与正常对照组相比差异无统计学意义（尸〉0．05）。②p-／t．P13Kp85tt、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、JP〈0．01）和GK．假手术组（分别尸〈0．01、P〈0．05、P〈0．01）均分别明显上升。③骨骼肌组织中P13Kp85ct、Akt／PKB及GLUT4mRNA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〈0．0l、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P13Kp85a、Akt／PKBmRNA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。

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

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.