Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Japan.
Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
Peptides. 2018 Aug;106:59-67. doi: 10.1016/j.peptides.2018.06.009. Epub 2018 Jun 30.
Since short bowel syndrome (SBS) patients face life-threatening conditions, the development of therapeutic strategies to induce intestinal adaptation has been investigated. Ghrelin, a ligand of growth hormone (GH) secretagogue-receptor that stimulates the release of GH and insulin like growth factor-1 (IGF-1), has several pleiotropic effects. We investigated whether ghrelin induces intestinal adaptation in parenterally fed rats with SBS.
Sprague-Dawley rats underwent venous catheterization and were divided into 3 groups: those receiving 90% small bowel resection while leaving the proximal jejunum and distal ileum (90% SBR) with TPN (SBS/TPN group), those receiving 90% SBR with TPN + ghrelin (SBS/TPN/ghrelin group), and those receiving sham operation and fed chow (sham group). Ghrelin was administered intravenously at 10 μg/kg/day. On Day 13, the rats were euthanized and the small intestine harvested, and the histology and crypt cell proliferation rates (CCPR), apoptosis, and nutrient transporter protein levels were analyzed and the plasma hormones were measured.
The villus height and crypt depth of the ileum in the SBS/TPN/ghrelin group were significantly higher than in the SBS/TPN group. The CCPR of the jejunum and the ileum significantly increased by the administration of ghrelin; however, the apoptosis rates did not significantly differ between the SBS/TPN and SBS/TPN/ghrelin groups. Significant differences did not exist in the plasma IGF-1 and nutrient transporter protein levels among three groups.
The intravenous administration of ghrelin stimulated the morphological intestinal adaptation of the ileum to a greater degree than the jejunum due to the direct effect of ghrelin.
由于短肠综合征（SBS）患者面临危及生命的情况，因此已经研究了开发诱导肠适应的治疗策略。Ghrelin 是生长激素（GH）分泌素受体的配体，可刺激 GH 和胰岛素样生长因子-1（IGF-1）的释放，具有多种多效性作用。我们研究了 ghrelin 是否会诱导 SBS 接受肠外营养的大鼠的肠适应。
Sprague-Dawley 大鼠接受静脉置管，并分为 3 组：接受近端空肠和远端回肠保留的 90%小肠切除术（90% SBR）和 TPN（SBS/TPN 组），接受 90% SBR 和 TPN+ghrelin（SBS/TPN/ghrelin 组），以及接受假手术和喂养标准饲料的（sham 组）。Ghrelin 以 10μg/kg/天的剂量静脉给药。在第 13 天，处死大鼠并取出小肠，分析组织学和隐窝细胞增殖率（CCPR）、凋亡和营养转运蛋白水平，并测量血浆激素。
SBS/TPN/ghrelin 组回肠的绒毛高度和隐窝深度明显高于 SBS/TPN 组。ghrelin 的给药显著增加了空肠和回肠的 CCPR；然而，SBS/TPN 和 SBS/TPN/ghrelin 组之间的凋亡率没有显著差异。三组之间的血浆 IGF-1 和营养转运蛋白水平没有显著差异。
ghrelin 的静脉给药通过 ghrelin 的直接作用，刺激回肠的形态学肠适应程度大于空肠。
