Department of Surgery, University of Wisconsin-Madison, USA.
Am J Physiol Gastrointest Liver Physiol. 2012 Sep 1;303(5):G610-22. doi: 10.1152/ajpgi.00184.2012. Epub 2012 Jun 28.
Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.
胰高血糖素样肽-2（GLP-2）是一种依赖于营养的、前胰高血糖素衍生的肠激素，对治疗短肠综合征（SBS）有一定效果。我们的目的是研究在一种模拟严重人类 SBS 并需要肠外营养（PN）的大鼠模型中，联合使用 GLP-2 和肠内营养（EN）如何影响肠道适应。雄性 Sprague-Dawley 大鼠被分为五组中的一组，并接受 PN 治疗 18 天：全肠外营养（TPN）单独、TPN+GLP-2（100μg·kg-1·d-1）、PN+EN+GLP-2（7 天）、PN+EN+GLP-2（18 天）和非手术口服参考组。动物接受了大量的远端肠切除术，然后进行空肠结肠吻合术和颈静脉导管放置。从术后第 4 天开始，EN 组的大鼠可以自由摄入 EN。从术后第 6 天开始，接受 PN+EN+GLP-2 的大鼠每天减少 0.25ml PN。与 TPN±GLP-2 相比，接受 PN+EN+GLP-2 的大鼠体重增加明显更多，能量摄入相似，PN 减少了 80%。接受 PN+EN+GLP-2 治疗 7 天或 18 天的大鼠体重增加、残留空肠长度和消化能力相似。接受 PN+EN+GLP-2 治疗的大鼠空肠 GLP-2 受体（GLP-2R）、胰岛素样生长因子-I（IGF-I）和 IGF 结合蛋白-5（IGFBP-5）表达增加。给予 TPN+GLP-2 治疗可增加空肠表皮生长因子的表达。停止 GLP-2 治疗 7 天后继续给予 EN，与 PN+EN+GLP-2 治疗 18 天相比，可维持大多数肠道适应，显著增加结肠前胰高血糖素的表达，并增加血浆 GLP-2 浓度，与单独 TPN 相比。总之，EN 通过改善体重增加来增强 GLP-2 的肠营养作用，允许在大鼠远端肠切除术后安全减少 80%的 PN，同时增加空肠 GLP-2R、IGF-I 和 IGFBP-5 的表达。
