中国普外基础与临床杂志

中国普外基础与临床杂志

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

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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。

ObjectiveTo 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). MethodsThirty 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 PI3Kp85α, Akt/PKB, and GLUT4 levels were measured by ELISA, Western blot, and real-time PCR me-thods, respectively. Results①Compared with the GK-SO group and GK-control group, the plasma ghrelin levels were significantly increased in the normal control group (P < 0.01) and GK-RYGB group (P < 0.01).②Compared with the GK-SO group and GK-control group, p-/t-PI3Kp85α, p-/t-Akt/PKB, and m-/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).③Compared with the GK-SO group and GK-control group, PI3Kp85α, 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). ConclusionRYGB could elevate the ghrelin level obviously and upregulate PI3Kp85α, 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; PI3K-Akt/PKB通路

Key words: Skeletal muscles insulin resistance; Roux-en-Y gastric bypass surgery; Ghrelin; PI3K-Akt/PKB passway

引用本文: 王勇, 白洁, 匡立润, 刘金钢. 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. 中国普外基础与临床杂志, 2014, 21(2): 162-167. doi: 10.7507/1007-9424.20140037 复制

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