Roux-en-Y胃转流术后肥胖大鼠胰岛β细胞增生及其机制研究

发布时间：2018-04-08 18:26

本文选题：肥胖　切入点：糖尿病　出处：《重庆医科大学》2017年硕士论文

【摘要】：目的:探讨Roux-en-Y胃转流术(Roux-en-Y gastric bypass,RYGB)后肥胖大鼠胰岛β细胞质量的改变及其机制,初步明确RYGB改善肥胖大鼠糖代谢的可能机制,为临床上通过RYGB治疗肥胖伴糖尿病患者提供理论依据。方法:(1)SD大鼠共46只,随机选取其中40只,高脂饲料喂养,建立肥胖大鼠模型,其余6只大鼠,给予普通低脂饲料,作为正常对照组(NCD组,n=6)。各大鼠单笼饲养共16周,并于每周同一时间测量体重。(2)16周末成功诱导22只大鼠肥胖,随后将大鼠随机分为:肥胖组(HFD组,n=6)、RYGB手术组(RYGB组,n=10)、假手术组(SHAM组,n=6)。手术前后分别记录大鼠体重。(3)术后6周末行葡萄糖耐量实验,ELISA测定空腹及餐后30min血清胰岛素和C肽水平,并同时计算HOME-IR。(4)术后8周末DEXA测定大鼠体脂率,收取大鼠附睾脂肪和胰腺组织并称重,ELISA测定空腹血清GLP-1水平,大鼠胰腺组织行胰岛素免疫组化染色,观察胰腺形态学改变。胰岛素免疫荧光染色评估β细胞质量改变情况。结果:(1)每组成功建模6只,16周末HFD组大鼠体重、附睾脂肪质量、体脂率较NCD组明显增加。术后8周,相较HFD组和SHAM组,RYGB组大鼠体重、附睾脂肪质量、体脂率明显下降(均P0.05)。(2)相较NCD组,HFD组大鼠空腹、餐后血糖,空腹胰岛素水平,HOME-IR明显升高。相较HFD组和SHAM组,RYGB组大鼠空腹、餐后血糖,空腹胰岛素水平明显降低,餐后胰岛素、C肽水平明显升高,HOME-IR明显下降(均P0.05)。(3)免疫组织化学染色示NCD组、RYGB组胰岛素阳性染色分布丰富,胰岛面积大,而HFD组、SHAM组胰岛素染色阳性区域零星分布。(4)术后大鼠胰腺质量-体质量比、胰腺组织中相对b细胞面积、b细胞质量、单位面积内胰岛数量,RYGB组均较HFD组、SHAM组明显增加(均P0.05),b细胞平均面积、平均胰岛面积各组间无明显差异(P(29)0.05)。(5)术后8周末RYGB组大鼠空腹GLP-1水平明显高于HFD组和SHAM组(P0.05)。结论:(1)高脂饮食诱导肥胖,糖代谢受损,并伴有胰岛素抵抗。(2)RYGB术后肥胖大鼠胰岛b细胞增生,细胞质量增加,胰岛数量增多,同时大鼠糖代谢及胰岛功能明显改善,其机制可能与血清GLP-1水平升高有关。
[Abstract]:Objective: to investigate the changes and mechanism of islet 尾 cell quality in obese rats after Roux-en-Y gastric bypass operation (Roux-en-Y gastric BYGB), and to clarify the possible mechanism of RYGB in improving glucose metabolism in obese rats, and to provide a theoretical basis for the clinical treatment of obese rats with diabetes by RYGB.Methods A total of 46 Sprague-Dawley rats were selected randomly, 40 of them were fed with high fat diet to establish the obese rat model. The other 6 rats were fed with normal low-fat diet as the normal control group.The serum insulin and C-peptide levels of fasting and postprandial 30min were measured by Elisa at the end of 6 weeks after operation. The body fat rate of rats was measured by DEXA at the end of 8 weeks after operation.The fat and pancreatic tissues of epididymis of rats were collected and the fasting serum GLP-1 levels were measured by weighing Elisa. The pancreatic tissues of rats were stained with insulin immunohistochemical staining to observe the morphologic changes of pancreas.Insulin immunofluorescence staining was used to evaluate the changes of 尾-cell quality.Results (1) six HFD rats in each group were successfully modeled at the end of 16 weeks. The body weight, mass of epididymal fat and body fat rate of each group were significantly higher than those of NCD group.At 8 weeks after operation, the body weight, mass of epididymis fat and body fat rate of rats in HFD group and SHAM group were significantly lower than those in NCD group (P0.05. 0. 2). The fasting postprandial blood glucose and fasting insulin level were significantly higher than those in NCD group.The area of pancreatic islets was large, but the distribution of insulin staining positive area in HFD group was scattered. 4) the ratio of pancreas mass to body mass and the relative area of b cells in pancreatic tissue were measured after operation.The number of islets per unit area in RYGB group was significantly higher than that in HFD group (P 0.05), and there was no significant difference in mean islet area among groups. The fasting GLP-1 level in RYGB group was significantly higher than that in HFD group and SHAM group at the end of 8 weeks after operation.Conclusion 1) High fat diet induced obesity, impaired glucose metabolism, and accompanied by insulin resistance. RYGB, the pancreatic islet b cells proliferated, cell mass increased, the number of islets increased, and the glucose metabolism and islet function of the obese rats improved significantly.The mechanism may be related to the increase of serum GLP-1 level.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R589.2;R656.6

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