Roux-en-Y胃旁路术后不同能量摄取对小肠结构功能及肠源性GLP-1分泌的影响

Roux-en-Y gastric bypass (RYGB) has been shown to markedly induce T2DM resolution, and one classical mechanism is the hindgut hypothesis. The essence of hindgut hypothesis is that RYGB produces both a gastric volume restriction and a changed alimentary tract anatomy, therefore, it is recognized that less digested chyme is routed closer to the ileum; nutrient activation of L endocrine cells with secretion such as GLP-1 in the ileum would be greater in RYGB. However, according to the results of our follow-up, we find that patients only eat less in general, or if they also choose different types of foods to eat after RYGB. Some RYGB patients have reported that they eat fewer sweet or fatty foods. Undoubtedly, the change of samll intestinal structure, function and enterogenous GLP-1 secretion in this condition of organic negative energy balance after RYGB is not clear. Therefore, on the basis of hindgut hypothesis which mainly emphasize intestinal anatomy rather than its function, we assumed that: ①The small intestinal motility would be slower after RYGB so as to increase the exposure time of intestinal mucosa to food;②The small intestinal mucosa would become hypertrophy with cell proliferation in order to strengthen the process of nutrient absorption;③The concentration of bile acid would be elevated under low fat diet. All of the above changes could exaggerate the secretion of enterogenous GLP-1. In this study, we use diabetes rats as the material. Through applying different energy intake by modulating the volume and content of food after RYGB, the changes of the GLP-1 secretion, small intestinal motility, the exposure time of small intestine to food,the concentration of bile acid in circulation and feces, as well as the microstructure and ultrastructure of different small intestinal limbs are observed. Furthermore,different techniques are utilized to change the small intestinal motility,the concentration of bile acid as well as the structure of small intestine, the GLP-1 secretion is detected and recorded accordingly. With the above results, we intend to elucidate the mechanism of intestinal function including small intestinal motility, bile acid, and intestinal structures by which RYGB resolute type 2 diabetes mellitus with over augmentation of endogenous GLP-1.

后肠假说是胃旁路手术（RYGB）治疗糖尿病的理论依据之一，它强调手术改变消化道解剖顺序，食物通过短路提前接触回肠L细胞促进GLP-1分泌缓解糖尿病。但申请人发现RYGB术后患者摄食量及油腻食物均减少，而机体这种负能量平衡状态对小肠结构功能及GLP-1分泌的调控作用均不明确。在后肠假说"重解剖、轻功能"基础上，我们提出：①RYGB术后小肠动力呈快进慢出型改变，食物接触小肠时间延长；②负能量平衡状态诱发小肠粘膜肥厚、肠内分泌细胞增殖以增强营养吸收过程；③少油腻饮食影响肠道胆汁酸浓度，而上述功能变化均为RYGB术后影响GLP-1分泌的非解剖因素。本研究以糖尿病大鼠为参照，在RYGB术后通过长期投食改变机体能量摄取，观察GLP-1分泌的变化，对比小肠动力、食物接触小肠时间、胆汁酸浓度和小肠结构的变化；进一步改变小肠动力、胆汁酸浓度及小肠结构，探讨其对GLP-1分泌的影响，对后肠假说进行补充和完善。

虽然Roux-en-Y胃旁路手术能有效缓解病态肥胖症，并快速发展成为肥胖合并2型糖尿病的有效治疗方式，但需要强调的是：RYGB手术缓解2型糖尿病的机理仍不清楚，尚需进一步阐明。本研究围绕三种不同饮食能量喂养下，RYGB手术对糖尿病大鼠胆汁酸代谢、胃肠激素分泌、糖耐量及胰岛素抵抗的影响来深入阐明RYGB手术治疗糖尿病的机理。大鼠随机分为GK大鼠+RYGB手术组，GK大鼠+假手术组及非糖尿病大鼠观察组，以不同能量（低碳水化合物、高碳水化合物及高脂肪三种不同的饮食）各喂养三组大鼠12周，检测每组大鼠血清及粪便胆汁酸水平，检测胃肠激素GLP-1、GIP、PYY水平及胰岛素抵抗状态。我们研究发现，RYGB手术与粪便及血清中胆汁酸水平的升高密切相关，且影响肝脏胆汁酸的下调。其次，RYGB上调GLP-1及PYY浓度，下调GIP浓度；显著改善了大鼠口服糖耐量及胰岛素抵抗。此外，三种不同能量的饮食喂养在GK大鼠+RYGB手术组，GK大鼠+假手术组及非糖尿病大鼠观察组中引起了不同的反应。在GK大鼠+RYGB手术组，高碳水化合物及高脂肪饮食引发了高胆汁酸水平，高GIP、PYY浓度及高胰岛素抵抗，并降低了GLP-1的浓度。这提示不同组成的饮食及不同能量的饮食均会影响RYGB术后糖尿病大鼠胆汁酸代谢及胰岛素抵抗状态。