Lai Sarah W, de Heuvel Elaine, Wallace Laurie E, Hartmann Bolette, Holst Jens J, Brindle Mary E, Chelikani Prasanth K, Sigalet David L
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
PLoS One. 2017 Jul 24;12(7):e0181453. doi: 10.1371/journal.pone.0181453. eCollection 2017.
To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats.
GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear.
Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition.
Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss.
Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.
确定外源性胰高血糖素样肽-2（GLP-2）在有或无大量远端肠切除的情况下，对大鼠空肠黏膜、肠神经元、肠道激素及组织储备适应性的影响。
GLP-2是一种已知对小肠黏膜有营养作用且能模拟短肠综合征（SBS）中肠道适应性变化的肠道激素。然而，外源性GLP-2和SBS对肠神经元的影响尚不清楚。
将Sprague Dawley大鼠随机分为四种处理组：横断肠组（TB）（n = 8）、TB + GLP-2（2.5 nmol/kg/h，n = 8）、SBS组（n = 5）或SBS + GLP-2（2.5 nmol/kg/h，n = 9）。SBS组接受60%空肠回肠切除并切除盲肠，行空肠结肠吻合术。所有大鼠接受肠外营养7天。测量的参数包括肠道形态学、己糖转运蛋白（SGLT-1、GLUT-2、GLUT-5）和GLP-2受体mRNA的qPCR、神经元全层免疫组织化学（HuC/D、VIP、nNOS）、血糖、肠道激素和身体组成。
切除增加了nNOS免疫阳性肌间神经元的比例、肠固有肌层厚度和隐窝细胞增殖，GLP-2治疗未重现这些变化。外源性GLP-2增加空肠黏膜表面积，而不影响肠VIP或nNOS神经元免疫阳性，减轻切除引起的空肠己糖转运蛋白丰度降低（SGLT-1、GLUT-2），增加血浆胰淀素并降低肽YY浓度。外源性GLP-2减轻切除引起的血糖升高和体脂丢失。
外源性GLP-2刺激空肠适应性变化，独立于肠神经元VIP或nNOS的变化，且对血浆胰淀素和肽YY浓度有不同影响。外源性GLP-2调节切除引起的外周葡萄糖和脂质储备变化的新能力，可能对理解肠切除后的全身反应很重要，值得进一步研究。
