Kaji Tatsuru, Tanaka Hiroaki, Redstone Heather, Wallace Laurie E, Holst Jens J, Sigalet David L
Division of Pediatric General Surgery, Institution of Infection Immunity and Inflammation, Faculty of Medicine, University of Calgary, Health Science Center, Calgary, Alberta, Canada.
J Surg Res. 2009 Apr;152(2):271-80. doi: 10.1016/j.jss.2008.05.007. Epub 2008 Jun 2.
We investigated the effects of variations in the postresection timing of glucagon-like peptide-2 (GLP-2) administration on intestinal morphology and activity.
A rat model of 90% intestinal resection (SBR) with exclusively parenteral nutritional (TPN) was used. Early versus late postresection GLP-2 stimulation was compared between SBR + TPN alone, SBR + TPN + GLP-2 (first wk), and SBR + TPN + GLP-2 (second wk) (n = 8/group). On d 14, animals were sacrificed and remnant ileum analyzed for morphology, crypt cell proliferation index (CPI), apoptosis index (API), and nutrient transporter expression (SGLT-1, GLUT-2, GLUT-5). In a separate study, the resection-induced effect on acute GLP-2 responsiveness was studied at d 3 and 10, in control or SBR animals, both supported with TPN. (n = 6).
Bowel length, weight, and width were increased in SBR + TPN + GLP-2 (first wk) compared with the SBR + TPN alone and SBR + TPN + GLP-2 (second wk) groups. Animal weight, villus height, total mucosal surface area, and CPI increased in both GLP-2 treated groups compared with the SBR + TPN group. Villus height and crypt depth effects were most pronounced in the SBR + TPN + GLP-2 (second wk) group. Increased expression of mRNA for the GLP-2 receptor was noted at d 3, declining below baseline by d 10, however this was not correlated with GLP-2 activation of enteric neurons. Exogenous GLP-2 increased the activation of submucosal neurons at d 3 in controls; resected animals had a higher baseline activity, but exogenous GLP-2 did not activate this further at either d 3 or 10 postresection.
GLP-2 effects on intestinal growth are maximal in the early postresection period and are associated with an apparent increase in expression of the receptor but no increase in neuronal activation. This suggests that the intestinal adaptive and growth promoting actions of GLP-2 may be mediated by non-neuronal effector pathways. Although further studies are required, early treatment with GLP-2 following resection may maximize intestinal growth.
我们研究了胰高血糖素样肽-2（GLP-2）给药的切除后时间变化对肠道形态和活性的影响。
采用仅接受肠外营养（TPN）的90%肠道切除（SBR）大鼠模型。比较单独的SBR + TPN、SBR + TPN + GLP-2（第一周）和SBR + TPN + GLP-2（第二周）组（每组n = 8）切除后早期与晚期GLP-2刺激的情况。在第14天，处死动物并分析残余回肠的形态、隐窝细胞增殖指数（CPI）、凋亡指数（API）和营养转运蛋白表达（SGLT-1、GLUT-2、GLUT-5）。在另一项研究中，在第3天和第10天研究切除对急性GLP-2反应性的影响，研究对象为接受TPN支持的对照或SBR动物（n = 6）。
与单独的SBR + TPN组和SBR + TPN + GLP-2（第二周）组相比，SBR + TPN + GLP-2（第一周）组的肠长度、重量和宽度增加。与SBR + TPN组相比，两个GLP-2治疗组的动物体重、绒毛高度、总粘膜表面积和CPI均增加。绒毛高度和隐窝深度的影响在SBR + TPN + GLP-2（第二周）组最为明显。在第3天观察到GLP-2受体的mRNA表达增加，到第10天降至基线以下，但这与GLP-2对肠神经元的激活无关。外源性GLP-2在第3天增加了对照组粘膜下神经元的激活；切除动物的基线活性较高，但外源性GLP-2在切除后第3天或第10天均未进一步激活。
GLP-2对肠道生长的影响在切除后早期最大，且与受体表达的明显增加相关，但神经元激活无增加。这表明GLP-2的肠道适应性和促生长作用可能由非神经元效应途径介导。尽管需要进一步研究，但切除后早期用GLP-2治疗可能使肠道生长最大化。
