不同区段胃肠转流术对2型糖尿病大鼠的治疗效果及胰岛素抵抗影响的实验研究

发布时间：2018-04-14 18:06

本文选题：胃转流术 + 手术方式　；参考：《皖南医学院》2015年硕士论文

【摘要】：目的:比较不同区段小肠转流的胃转流手术对2型糖尿病的治疗效果及胰岛素抵抗的影响,通过分析四组大鼠手术处理前后空腹血糖水平、胰岛功能、体质量的的变化以及各组大鼠术后营养不良的发生率来判断小肠转流的最佳效应区域。方法:32只8~10周龄体重相近的雄性GK大鼠随机分成4组,每组8只。第1组:对照组,胃十二指肠离断后在吻合;第2组:十二指肠转流组,保留全胃行十二指肠旷置;第3组:空肠转流组,保留全胃行十二指肠加空肠旷置;第4组:回肠转流组,保留全胃行十二指肠加空、回肠旷置。分别术前与术后第1、3、6、12周获取大鼠眼眶后静脉血,采用血糖仪、电子秤动态测定四组动物血液中空腹血糖水平和动物体质量;酶联免疫吸附试验(ELISA)检测各组大鼠手术前后血清胰岛素、GLP-1的变化,最后计算胰岛素抵抗指数(HOMA—IR)。结果:全组32只大鼠的手术成功率90%,第4组大鼠术后3~4周时由于严重营养不良相继死亡。与术前和同时间点对照组比较,GBP手术组(2、3、4组)术后空腹血糖水平均有不同幅度的下降,至术后12周时第2组空腹血糖水平由14.98±2.17下降至5.23±0.70,差异有统计学意义(PO.05);第3组空腹血糖水平由15.20±1.92下降至5.29±0.42,差异有统计学意义(PO.05);其中以第3组尤为显著。与术前相比,术后第1周各组(除第4组)GK大鼠的体质量略有上升,第3、6、12周除第4组外其他各组大鼠体质量均明显增加,第4组大鼠体质量术后显著降低(PO.05)。与术前和同时间点对照组比较,GBP手术组(2、3、4组)术后1-3周空腹胰岛素水平升高,第6周开始略有下降,至12周明显下降;第2组由14.86±1.22下降至9.46±1.10m U/L,差异有统计学意义(PO.05);第3组由14.71±1.14下降至8.93±1.36m U/L,差异有统计学意义(PO.05);大鼠空腹胰岛素(FINS)经历了先升后降的过程,其中以第3组略为显著。与术前和同时间点对照组比较,GBP手术组(2、3、4组)术后1-3周大鼠胰岛素抵抗指数(HOMA-IR)略有下降,至12周时有明显下降;第2组HOMA-IR由9.97±1.95下降至2.21±0.38,差异有统计学意义(PO.05);第3组HOMA-IR由9.98±1.39下降至2.03±0.23,差异有统计学意义(PO.05);其中以第3组下降略为显著。与术前和同时间点对照组比较,GBP手术组(2、3、4组)术后GLP-1水平均有不同幅度的升高,至12周时达到最高,第2组GLP-1由9.38±1.88升高至18.96±3.42,差异有统计学意义(PO.05);第3组GLP-1由9.02±2.20升高至23.23±4.17,差异有统计学意义(PO.05);其中以第3组尤为显著。结论:1、保留全胃,旷置不同区段小肠的胃转流术式,能显著降低非肥胖的糖尿病大鼠空腹血糖和胰岛素抵抗,且与大鼠的体质量增减无关。2、术后食物提前进入末端回肠,导致末端回肠细胞分泌的胰高血糖素样肽-1增多,说明GLP-1的增加可能是GBP术治疗T2DM原因之一。3、小肠转流的最佳效应区域位是小肠中段,提示在临床GBP术式中,小肠最佳转流效应部位可能为小肠中段,即空肠与回肠交界处为宜。
[Abstract]:Objective: to compare the effect of gastric bypass in different sections of small intestine bypass on type 2 diabetes mellitus and the effect of insulin resistance, and to analyze the fasting blood glucose level and pancreatic islet function before and after operation in four groups of rats.The changes of body mass and the incidence of malnutrition in each group were used to determine the optimal effect area of small intestinal bypass.Methods 32 male GK rats of 10 weeks old were randomly divided into 4 groups with 8 rats in each group.Group 1: control group, gastroduodenal devascularization after anastomosis, group 2: duodenal bypass group, total gastric duodenal open place, group 3: jejunal bypass group, total gastric duodenum plus jejunum open place;Group 4: ileal bypass group.Blood samples of posterior orbital vein were obtained from rats before operation and at 612 weeks after operation. Fasting blood glucose level and animal mass in the blood of the four groups were dynamically measured by blood glucose meter and electronic scale.The changes of serum insulin GLP-1 were measured before and after operation by Elisa, and the insulin resistance index (HOMA-IRI) was calculated.Results: the successful rate of operation was 90% in 32 rats in the whole group. The rats in group 4 died of severe malnutrition 3 weeks after operation.Compared with the control group before operation and at the same time, the fasting blood glucose level in the GBP operation group decreased by different extent after operation.At 12 weeks after operation, the fasting blood glucose level in the second group decreased from 14.98 卤2.17 to 5.23 卤0.70, and the fasting blood glucose level in the third group decreased from 15.20 卤1.92 to 5.29 卤0.42, especially in the third group.Compared with pre-operation, the body mass of rats in each group (except group 4) increased slightly at the 1st week after operation, and increased significantly at week 3, 6 and 12 except group 4, and the body mass of group 4 decreased significantly after operation.Compared with the control group before operation and at the same time, the fasting insulin level in the GBP operation group increased 1-3 weeks after operation, decreased slightly at the 6th week, and decreased significantly at the 12th week.Group 2 decreased from 14.86 卤1.22 to 9.46 卤1.10mU / L, and group 3 decreased from 14.71 卤1.14 to 8.93 卤1.36mUL, the difference was statistically significant.Compared with the control group before operation and at the same time point, the insulin resistance index (HOMA-IRI) of rats in GBP operation group decreased slightly 1-3 weeks after operation, and decreased significantly at 12 weeks.The HOMA-IR of the second group decreased from 9.97 卤1.95 to 2.21 卤0.38, the difference was statistically significant, and the HOMA-IR of the third group decreased from 9.98 卤1.39 to 2.03 卤0.23, the difference was statistically significant, especially in the third group.Compared with the control group before operation and at the same time, the level of GLP-1 increased in different amplitude after operation, and reached the highest level at 12 weeks.The GLP-1 of the second group was increased from 9.38 卤1.88 to 18.96 卤3.42, the difference was statistically significant (P < 0.05), the GLP-1 of the third group was increased from 9.02 卤2.20 to 23.23 卤4.17, the difference was statistically significant, especially in the third group.Conclusion the gastric bypass method of keeping the whole stomach and leaving different sections of the small intestine can significantly reduce the fasting blood glucose and insulin resistance in non-obese diabetic rats, and have no relation with the increase or decrease of the body weight of the rats. The food enters the terminal ileum in advance after operation.The increase of glucagon-like peptide-1 secreted by terminal ileal cells suggests that the increase of GLP-1 may be one of the causes of T2DM treated by GBP. The best effect area of small intestinal bypass is the middle part of small intestine, which suggests that the increase of GLP-1 may be one of the causes of T2DM by GBP.The best bypass site of the small intestine may be the middle part of the small intestine, that is, the junction between the jejunum and the ileum.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1;R656.6

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