不同食物对肠旁路术后GK大鼠血糖的影响及机制研究

At present, there is a high incidence of type 2 diabetes and it can not be cured by medicine.In recent years, the study found that Roux-en-Y gastric bypass which makes diversion of the bile and pancreatic juice and change the digestion pathway could alleviate type 2 diabetes. In our previous study in GK rats ,we found that new biliopancreatic diversion did not change the digestion pathway, and only postponed the time and location of food mixing with the bile and pancreatic juice, while also improving glucose tolerance in GK rats. This research proposed to study the possible mechanisms of surgical treatment for type 2 diabetes, to explore the contribution of improving glucose tolerance by the changes in gut hormone and the digestion and absorption function. This study includes, (1)establish the model of duodenal-jejunal bypass and biliary pancreatic diversion in GK rats；（2）intragastric administration by carbohydrate,protein, lipid and mixed food then detect the levels of glucose, blood lipids and gut hormone,then analyze the relationship among the blood glucose,blood lipids and gut hormone；（3）measure intestinal carbohydrate absorption by oral D-xylose loading test and fat absorption by fecal fat measurement；(4)observe the levels of blood glucose,blood lipids and gut hormone in 9 months postoperative period. Study on changes in morphological anatomy of intestine, the gut hormone secretion function and the fibrosis in pancreatic islet. Through the above researches could be supplied as experiment and theory foundations on surgical treatment for type 2 diabetes.

2型糖尿病发病率高，终生需要药物治疗。临床发现，转流胆胰液和旷置十二指肠的胃旁路术可以治疗2型糖尿病。我们先前用糖尿病模型鼠（GK大鼠）的研究发现，仅转流胆胰液，不旷置十二指肠，也可以降低血糖。为了研究胃肠旁路手术的降糖机制，探讨胃肠激素变化和消化功能变化在其中的作用，我们设计了本课题。具体研究内容包括：（1）建立GK大鼠肠旁路模型和胆胰转流模型；（2）分别用糖类、蛋白类、脂类和混合食物灌胃，检测灌胃后血糖、血脂、胃肠激素等水平变化，分析术后不同类食物对GK大鼠血糖、血脂、胃肠激素的影响及相互间的关系；（3）通过口服木糖负载实验及对粪脂检测，分析糖类及脂类的吸收情况。（4）观察术后9个月间GK大鼠的血糖、血脂及胃肠激素的情况，并研究其肠道的解剖形态和肠道分泌胃肠激素功能的变化及胰腺纤维化情况。希望本课题研究能为外科治疗2型糖尿病提供理论和实验依据。

研究背景：近年来, RYGB等减肥手术治疗2型糖尿病的效果已被大量临床及基础实验证实。然而对其机制目前尚无明确定论。.研究一：改良胆胰转流术对GK大鼠血糖和血脂的影响.方法：将GK大鼠随机分为3组,分别行十二指肠-空肠旁路术(duodenal-jejunal bypass,DJB)、改良胆胰转流术(new biliopancreatic diversion,NBPD)和假手术。检测各组术前及术后体质量、随机血糖(random plasma glucose)、空腹血糖(fastingplasma glucose, FPG)、血脂及胰岛素水平。.结果：术后1 wk, NBPD组、DJB组大鼠随机血糖明显低于假手术组, 差异均有统计学意义(P <0.05); 术后4 wk, DJB组、NBPD组空腹胆固醇比之术前明显下降, 差异有统计学意义。.结论: DJB和NBPD术式可以降低GK大鼠血糖、血脂, 其原因可能是术后胆胰液的转流造成食物尤其是脂类的消化吸收不完全, 改善了脂代谢, 进而降低血糖。..为了进一步研究DJB与NBPD具体的降糖机制及糖类、脂质的消化吸收情况，我们还设计了另一个实验。.实验二：十二指肠-空肠转流术和改良胆胰转流术对2型糖尿病.大鼠模型血糖、血脂、肠道激素的影响.方法：将成模2型糖尿病大鼠随机分为3组, 分别行DJB、NBPD及假手术。检测各组术前及术后血糖及血脂。并对术后的各组大鼠行三大营养物质灌胃，检测灌胃前后血糖、血浆肠抑胃肽（GIP）、胰高血糖素样肽-1（GLP-1）。.结果：.④淀粉灌胃后30min，DJB组血浆GLP-1水平高于NBPD组、假手术组，差异有统计学意义。.⑤脂肪乳及花生油灌胃后三组大鼠FFA、TG均升高，DJB组和NBPD组与假手术相比差异具有统计学意义（P<0.05）。.⑥花生油灌胃后30min，DJB组和NBPD组血浆GLP-1水平高于假手术组，差异有统计学意义。.结论：①DJB术后由于有肠道旷置和胆胰液转流可能导致肠道分泌GLP-1明显增加，进而促进胰岛素分泌，这可能是降糖机制之一。.②DJB组和NBPD组均可以影响脂类的消化和吸收，可能是其降糖机制之一。其中血脂的改善主要与胆胰液的转流有关。