十二指肠空肠旁路术对2型糖尿病大鼠肠道糖代谢及血糖控制的影响
发布时间：2018-09-10 21:31
【摘要】：目的:Roux胃旁路(Roux-en-Y gastric bypass,RYGB)能够持续减轻体重,同时可以长期、有效的控制血糖,然而Roux胃旁路术有严格的手术适应症,适用于肥胖的2型糖尿病(type 2 diabetes mellitus,T2DM)患者。十二指肠空肠旁路术(duodenal-jejunal bypass,DJB)作为Roux胃旁路术的改良术式,术后胃的解剖结构没有发生改变,而仅仅旷置了近端小肠,对非肥胖T2DM患者也取得了一定的治疗效果。本研究主要探讨DJB对T2DM大鼠的治疗效果,以及术后胃肠道激素和肠道糖代谢的改变,在血糖稳态改善中所起的作用,该研究将为手术方式的改良,以及在T2DM治疗过程中大力推广外科手术方式,提供坚实的理论依据。方法:1.SPF级雄性SD大鼠55只,利用随机数字表法,随机取40只作为高脂组(high-fat diet group,HFD),剩于15只为对照组(Control group,CON)。本研究采用高脂饲料喂养SD大鼠4周,并进行胰岛素耐量检测,以确定诱导出胰岛素抵抗。随后尾静脉注射链脲佐菌素(streptozocin,STZ),以诱导高血糖。采用血糖仪检测该T2DM大鼠模型空腹血糖和随机血糖,并分别于0周,4周和注射STZ后1周,采用ELISA方法测定其血清葡萄糖依赖性促胰岛素样多肽(gastric inhibitory polypeptide,GIP)的含量以及胰高血糖素样肽-1(glucagon-likepeptide1,GLP-1)水平。2.从造模成功的大鼠中,挑选血糖、体重较为均一的大鼠进行实验。按照随机数字法将其分为DJB组和假手术组(S-DJB),每组15只,于注射STZ后第2周进行相应手术。对照组继续普通饲料喂养,不进行任何干预。分别比较3组大鼠手术前后血糖、口服糖耐量、胰岛素耐量、体重和进食量的变化,以明确DJB对糖尿病大鼠的治疗效果。同时检测手术前后胰高血糖素、GLP-1和GIP水平的改变,以探究DJB改善糖代谢,与胃肠道激素的关系。3.于术后8周处死大鼠,取各组大鼠小肠及肠腔内容物,用生理盐水洗净肠腔,无菌纱布吸干水分后称其重量并观察大体形态。随后取其血清检测总胆固醇、甘油三酯和游离脂肪酸等血脂水平的变化;采用荧光定量PCR和Western Blotting等技术,检测术后Roux肠袢涉及糖代谢与脂代谢关键酶基因和蛋白水平的改变;采用定量PCR的方法,对小肠不同部位肠腔内容物中双歧杆菌、拟杆菌、普拉梭菌和乳酸杆菌数量进行检测。结果:1.STZ注射后3天,高脂组大鼠空腹血糖和随机血糖均显著高于对照组。造模过程中高脂组大鼠血清GIP水平逐渐升高,GLP-1水平逐渐降低,至注射STZ后1周与对照组相比有显著差异。2.术后8周,与S-DJB组相比,DJB组空腹血糖、血脂、口服糖耐量及胰岛素耐量均显著降低。DJB组空腹及餐后GLP-1水平均显著升高,餐后GIP水平显著降低,与S-DJB组相比有统计学差异,此外DJB组餐后胰高血糖素分泌显著降低,与自身空腹水平相比有统计学差异。3.术后8周,DJB组Roux肠袢重量约为S-DJB组3倍。DJB组大鼠小肠参与葡萄糖摄取和利用的关键酶m RNA及蛋白水平均显著升高,与S-DJB组相比有统计学差异。涉及胆固醇生物合成与摄取的关键酶m RNA及蛋白水平也显著升高。DJB术后随着营养物质的流动,小肠涉及葡萄糖和胆固醇摄取和利用的关键酶和因子的m RNA水平成梯度改变。升高最明显的是Roux肠袢,胆胰肠袢则没有发生显著差异,公共肠袢近端m RNA水平也显著升高,而远端变化不明显。DJB组Roux肠袢和公共肠袢双歧杆菌、拟杆菌、普拉梭菌的数量显著高于S-DJB组,而胆胰肠袢则没有发生显著改变。结论:1.DJB能显著改善T2DM大鼠糖代谢状态,其术后空腹血糖、口服糖耐量以及胰岛素耐量均显著改善,而体重和进食量则没有明显改变。2.胃肠道激素的改变,在T2DM发生发展过程中起到重要作用。同时DJB术后胃肠道激素的改变,在血糖稳态的调节中起到了重要的作用。3.DJB术后,Roux肠袢涉及糖代谢和胆固醇合成的关键酶基因和蛋白水平均显著增加。Roux肠袢重组肠道糖脂代谢,以满足术后肠道重塑对能量的需求,使得肠道成为术后机体葡萄糖处置的重要器官,对术后血糖的控制起到了重要作用。未消化的营养物质经过Roux肠袢,可能是触发肠道重塑和葡萄糖代谢重排列的原因。
[Abstract]:OBJECTIVE: Roux-en-Y gastric bypass (RYGB) can sustain weight loss and control blood glucose for a long time. However, Roux gastric bypass has strict surgical indications and is suitable for obese patients with type 2 diabetes mellitus (T2DM). The improved method of oux gastric bypass has not changed the anatomical structure of the stomach after operation, but only the proximal small intestine has been emptied. This study mainly discussed the therapeutic effect of DJB on non-obese T2DM rats, and the changes of gastrointestinal hormones and intestinal glucose metabolism after operation. Methods: Fifty-five SPF male SD rats were randomly selected as high-fat diet group (HFD) and 15 as control group (CON). The SD rats were fed with high-fat diet for 4 weeks, and insulin tolerance was tested to determine insulin resistance. Then the rats were injected with streptozocin (STZ) into the tail vein to induce hyperglycemia. Methods The serum levels of glucose-dependent insulin-like polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. The control group was fed with normal diet without any intervention. The changes of blood glucose, oral glucose tolerance, insulin tolerance, body weight and food intake were compared before and after operation in order to determine the therapeutic effect of DJB on diabetic rats. Glucagon, GLP-1 and GIP levels were changed to explore the relationship between DJB and gastrointestinal hormones. 3. Rats were sacrificed at 8 weeks after operation. The intestinal and intestinal contents of each group were washed with normal saline. The intestinal cavity was dried by sterile gauze and weighed and gross morphology was observed. Changes of serum lipids levels such as triesters and free fatty acids were detected by fluorescence quantitative PCR and Western Blotting. Changes of genes and protein levels of key enzymes involved in glycometabolism and lipid metabolism in Roux loops were detected after operation. Results: 1. Fasting blood glucose and random blood glucose were significantly higher in the hyperlipidemia group than in the control group at 3 days after STZ injection. The fasting and postprandial GLP-1 levels in DJB group were significantly higher than those in S-DJB group, and the postprandial GIP levels were significantly lower than those in S-DJB group. In addition, the postprandial glucagon secretion in DJB group was significantly lower than that in S-DJB group, and there was a statistically significant difference between DJB group and its own fasting level. The levels of M RNA and protein, the key enzymes involved in glucose uptake and utilization, were significantly higher in DJB group than in S-DJB group. The levels of M RNA of key enzymes and factors for cholesterol uptake and utilization were gradiently changed.The most obvious increase was in Roux intestinal loop,but no significant difference was found in biliopancreatic intestinal loop.The level of M RNA in proximal end of common intestinal loop was also significantly increased,but the distal end was not significantly changed.The number of bifidobacteria in Roux intestinal loop and common intestinal loop in DJB group was significant. Conclusion: 1. DJB can significantly improve the glucose metabolism in T2DM rats, and the fasting blood glucose, oral glucose tolerance and insulin tolerance are significantly improved, but the weight and food intake are not significantly changed. 2. The changes of gastrointestinal hormones play an important role in the development of T2DM. At the same time, the changes of gastrointestinal hormones after DJB play an important role in the regulation of blood glucose homeostasis. 3. After DJB, Roux intestinal loop involved in glucose metabolism and cholesterol synthesis of the key enzyme genes and protein levels were significantly increased. Roux intestinal loop reconstituted intestinal glycolipid metabolism to meet the energy requirements of intestinal remodeling after DJB, making the intestinal tract become Undigested nutrients pass through the Roux loop, which may trigger intestinal remodeling and rearrangement of glucose metabolism.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R656.6
[Abstract]:OBJECTIVE: Roux-en-Y gastric bypass (RYGB) can sustain weight loss and control blood glucose for a long time. However, Roux gastric bypass has strict surgical indications and is suitable for obese patients with type 2 diabetes mellitus (T2DM). The improved method of oux gastric bypass has not changed the anatomical structure of the stomach after operation, but only the proximal small intestine has been emptied. This study mainly discussed the therapeutic effect of DJB on non-obese T2DM rats, and the changes of gastrointestinal hormones and intestinal glucose metabolism after operation. Methods: Fifty-five SPF male SD rats were randomly selected as high-fat diet group (HFD) and 15 as control group (CON). The SD rats were fed with high-fat diet for 4 weeks, and insulin tolerance was tested to determine insulin resistance. Then the rats were injected with streptozocin (STZ) into the tail vein to induce hyperglycemia. Methods The serum levels of glucose-dependent insulin-like polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. The control group was fed with normal diet without any intervention. The changes of blood glucose, oral glucose tolerance, insulin tolerance, body weight and food intake were compared before and after operation in order to determine the therapeutic effect of DJB on diabetic rats. Glucagon, GLP-1 and GIP levels were changed to explore the relationship between DJB and gastrointestinal hormones. 3. Rats were sacrificed at 8 weeks after operation. The intestinal and intestinal contents of each group were washed with normal saline. The intestinal cavity was dried by sterile gauze and weighed and gross morphology was observed. Changes of serum lipids levels such as triesters and free fatty acids were detected by fluorescence quantitative PCR and Western Blotting. Changes of genes and protein levels of key enzymes involved in glycometabolism and lipid metabolism in Roux loops were detected after operation. Results: 1. Fasting blood glucose and random blood glucose were significantly higher in the hyperlipidemia group than in the control group at 3 days after STZ injection. The fasting and postprandial GLP-1 levels in DJB group were significantly higher than those in S-DJB group, and the postprandial GIP levels were significantly lower than those in S-DJB group. In addition, the postprandial glucagon secretion in DJB group was significantly lower than that in S-DJB group, and there was a statistically significant difference between DJB group and its own fasting level. The levels of M RNA and protein, the key enzymes involved in glucose uptake and utilization, were significantly higher in DJB group than in S-DJB group. The levels of M RNA of key enzymes and factors for cholesterol uptake and utilization were gradiently changed.The most obvious increase was in Roux intestinal loop,but no significant difference was found in biliopancreatic intestinal loop.The level of M RNA in proximal end of common intestinal loop was also significantly increased,but the distal end was not significantly changed.The number of bifidobacteria in Roux intestinal loop and common intestinal loop in DJB group was significant. Conclusion: 1. DJB can significantly improve the glucose metabolism in T2DM rats, and the fasting blood glucose, oral glucose tolerance and insulin tolerance are significantly improved, but the weight and food intake are not significantly changed. 2. The changes of gastrointestinal hormones play an important role in the development of T2DM. At the same time, the changes of gastrointestinal hormones after DJB play an important role in the regulation of blood glucose homeostasis. 3. After DJB, Roux intestinal loop involved in glucose metabolism and cholesterol synthesis of the key enzyme genes and protein levels were significantly increased. Roux intestinal loop reconstituted intestinal glycolipid metabolism to meet the energy requirements of intestinal remodeling after DJB, making the intestinal tract become Undigested nutrients pass through the Roux loop, which may trigger intestinal remodeling and rearrangement of glucose metabolism.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R656.6
【参考文献】
相关期刊论文 前5条
1 张巨彪;苏秀兰;欧阳晓晖;;1型糖尿病大鼠模型的建立及观察[J];医学综述;2013年02期
2 都敏;鲍兴;张杰;戴t熻，
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