胃旁路术后IRS-1和IRS-2的表达变化对糖尿病大鼠空腹血糖和胰岛素抵抗的影响及作用机制  

Influence and mechanism of the change of IRS-1 and IRS-2 expressions on fasting blood glucose and insulin resistance in diabetic rats after gastric bypass surgery

作　　者：李龙[1] 李宇[1] 周岩冰[1] 卢存龙[1] Li Long;Li Yu;Zhou Yanbing;Lu Cunlong(Department of General Surgery, the Affiliated Hospital of Qingdao University, Shandong 266000, China)

机构地区：[1]青岛大学附属医院普外科,山东266000

出　　处：《中华肥胖与代谢病电子杂志》2016年第4期219-224,共6页Chinese Journal Of Obesity and Metabolic Diseases：Electronic Edition

基　　金：山东省自然科学基金资助项目(ZR2012HM046)

摘　　要：目的探讨Roux-en-Y胃旁路术（RYGB）后胰岛素受体底物（IRS）-1和IRS-2的表达变化对糖尿病大鼠空腹血糖和胰岛素抵抗的影响及其作用机制。方法用随机数字表法将30只糖尿病模型的Wistar大鼠分为RYGB组、假手术组和饮食对照组。另选取10只同周龄的正常Wistar大鼠为对照组。RYGB组接受RYGB，假手术组在相同位置处切开胃壁和空肠后行原位缝合，饮食对照组的进食量为RYGB组前1天的进食量，空白对照组自由进食普通饲料。于术前和术后1、2、3、4周检测空腹血糖（FPG）和空腹胰岛素（FIns）水平，并计算胰岛素抵抗指数（HOMA-IR）。其后处死大鼠，取骨骼肌、肝脏和胰腺组织。采用Westernblot技术检测各组大鼠骨骼肌和肝脏中IRS-1和IRS-2的表达情况，采用免疫组化方法检测胰腺IRS-2的表达情况。4组数据的比较采用单因素方差分析，组间两两比较采用LSD-t检验；组内两组数据的比较采用配对t检验；4组胰腺组织IRS-2阳性表达率的比较采用χ2检验。结果术后第4周，RYGB组大鼠的FPG水平较术前明显降低（t=30.617，P＜0.05），低于同期的假手术组和饮食对照组（LSD-t假手术组=12.112，LSD-t饮食对照组=10.095，P值均＜0.05)，与空白对照组比较差异无统计学意义（LSD-t=0.347，P＞0.05）；RYGB组大鼠的HOMA-IR值也较术前明显下降（t=8.631，P＜0.05），低于同期假手术组和饮食对照组（LSD-t假手术组=7.713，LSD-t饮食对照组=7.931，P值均＜0.05），与空白对照组比较差异无统计学意义（LSD-t=0.822，P＞0.05）。手术4周后，RYGB组大鼠肌肉组织中IRS-1和其磷酸化的p-IRS-1表达水平明显高于假手术组和饮食对照组（P＜0.05）；RYGB组大鼠肝脏组织中IRS-2的表达水平明显低于假手术组和饮食对照组（P＜0.05），稍高于空白对照组；RYGB组大鼠胰腺细胞中IRS-2的阳性表达率为76%，明显高于饮食对照组的2%，Objective To investigate the influence and mechanism of the change of insulin receptor substrate (IRS)-1 and IRS-2 expressions on fasting plasma glucose and insulin resistance in diabetic rats after Roux-en-Y gastric bypass (RYGB). Methods Thirty diabetic Wistar rats were randomized into the RYGB group, sham operation group and diet control group by random number table method with 10 rats in each group, and 10 normal Wistar rats in the same weeks old were picked up as the blank control group. The rats in the RYGB group underwent RYGB, the rats in the sham operation group underwent the operation in which gastric wall and jejunum were cut and then sutured in the original locations, the food intake of the diet control group rats was as much as those of the RYGB group rats 1 day before, and the rats in the blank control group ate as much normal feedstuff as they liked. Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment of insulin resistance (HOMA-IR) were tested before and 1, 2, 3, 4 weeks after operation. Then all the rates were killed, their skeletal muscle, liver and pancreas were taken out.The expressions of IRS-1 and IRS-2 in the skeletal muscle and liver were detected by Western blot, and the expression of IRS-2 in the pancreas was detected by immunohistochemistry. The comparisons among the 4 groups were conducted using one-way ANOVA analysis, with LSD-t test for pairwise comparison; and the data between two sets in the same group were compared using t test; and the positive expression rates of IRS-2 in pancreas among 4 groups were compared using χ2 test. Results In the fourth week after operation, the FPG level of the RYGB group was significantly lower than that before operation (t=30.617, P<0.05), and also lower than that of the sham operation and diet control groups in the same period (LSD-t=12.112, 10.095,P<0.05); but had no statistical difference with that of the blank control group (LSD-t=0.347, P>0.05). In addition, the HOMA-IR level of the RYGB group was significantly lo

关 键 词：糖尿病 2型 ROUX-EN-Y胃旁路术 胰岛素受体底物 胰岛素抵抗 空腹血糖 

分 类 号：R587.1[医药卫生—内分泌]