不同Roux肠袢长度的十二指肠空肠旁路术对2型糖尿病模型大鼠糖代谢的影响

Effect of duodenal-jejunum bypass with different Roux limb lengths on the metabolism of type 2 diabetic rats

目的:探究不同Roux肠袢长度的十二指肠空肠旁路术(DJB)对2型糖尿病模型(Goto-Kakizaki,GK)大鼠术后体重、空腹血糖(FPG)与胰高血糖素样肽(GLP-1)的影响,并进一步探究GK大鼠的GLP-1相关受体在胃十二指肠吻合处、十二指肠残端屈氏韧带处以及共同通路空肠处的术后表达的情况及其相关机制。方法:采用抽签法将40只GK大鼠随机分成5组,每组8只。对照组离断十二指肠后重新吻合作为A组,手术组实施保留全胃的不同Roux肠袢长度的DJB,分别留取10、20、30和40cm的Roux肠袢作为B、C、D和E组。分别于术前3d及术后1、3、5、8周眼眶后采集静脉血,动态监测大鼠体重和FPG值变化,采用酶联免疫吸附法(ELISA)测定大鼠的GLP-1水平。8周后统一取出GK大鼠胃十二指肠吻合处、十二指肠残端屈氏韧带处以及共同通路空肠处三处标本,采用免疫组化法分析GLP-1受体的表达。结果:全组40只GK大鼠的手术成功率为72.5.%,保留40cm肠袢的E组术后1~5周相继死亡。与术后同时间点对照组相比,手术组在术后整个周期中体重改变不明显,差异无统计学意义(P>0.05)。与本组术前和术后同时间点对照组相比,所有DJB手术组术后FPG、GLP-1水平均下降(P<0.05);术后1、3周,手术组E组FPG、GLP-1水平较手术组B、C组下降明显(P<0.05);与对照组相比,DJB各手术组伴随Roux肠袢延长GLP-1受体在胃十二指肠处以及共同通路空肠处逐渐升高(P<0.05),而在十二指肠残端屈氏韧带处逐渐减少(P<0.05)。结论:DJB对GK大鼠有降糖效果,降糖效果随着Roux肠袢长度的延长而提高,其降低血糖的机制可能与GLP-1受体在各肠段的表达量相关,结果显示GLP-1受体在食物流经处的表达可能与Roux肠袢长度相关。

Objective:To explore the effect of duodenal-jejunum bypass (DJB) with different Roux limb lengths on the body weight, fasting plasma glucose (FPG), fasting glucagon-like peptide-1 (GLP-1), and GLP-1 receptor expression in type 2 diabetic (Goto-kakizaki,GK) rats and to explore the possible mechanism. Methods: Forty T2DM rats (GK rats) of 8-week old were randomly divided into five groups by lottery, 8 rats in each. The control group was re-anastomosed after duodenal dissection as group A, the surgery group performed DJB with different lengths of Roux limb (10,20,30,40 cm) as group B, C, D and E, respectively. Posterior orbit venous blood of rats were collected respectively 3 day before surgery and postoperative 1, 3, 5, 8 weeks, the body weight and FPG levels of each rat was detected dynamically, and the GLP-1 level was determined by enzyme-linked immunosorbent assay (ELISA). At 8 weeks after surgery, GLP-1 receptor expression in the gastroduodenal anastomotic position, duodenal stump position and common pathways jejunum position was analyzed by immunohistochemistry. Results: The success rate of operation of 40 GK rats was 72.5%, the group E of retained 40 cm Roux limb died during 1-5 weeks after surgery. Compared with the control group at the same time point after surgery, there was no significant change in body weight in the DJB group(P>0.05).Compared with the preoperative results and the control group at the same time point after surgery, FPG and GLP-1 levels in all DJB groups decreased after surgery(P<0.05).And 1,3 weeks after surgery, FPG and GLP-1 levels in group E decreased significantly compared with group B,C (P<0.05).Compared with the control group, GLP-1 receptor expression in the gastroduodenal anastomotic position and the common pathway jejunum position gradually increased (P<0.05), while decreased in the posterior flexor ligament of the duodenal stump postion (P<0.05) in each DJB surgery group. Conclusion: DJB has a hypoglycemic effect on GK rats, and the hypoglycemic effect increases with the prolongation of the length of Roux limb, and the mechanism of hypoglycemic effect may be related to the expression of GLP-1 receptor in each intestine segment, and the expression of GLP-1 receptor at the place where the food flowed through may be related to the length of Roux limb.