Kaji Tatsuru, Tanaka Hiroaki, Wallace Laurie E, Kravarusic Dragan, Holst Jens, Sigalet David L
Alberta Children's Hospital, Department of Surgery and Gastrointestinal Research Group, Institution of Infection Immunity and Inflammation, Faculty of Medicine, University of Calgary, Health Science Center, Calgary, Alberta, Canada.
J Pediatr Surg. 2009 Aug;44(8):1552-9. doi: 10.1016/j.jpedsurg.2008.10.001.
BACKGROUND/PURPOSE: The serial transverse enteroplasty (STEP) procedure appears beneficial clinically, but the mechanism(s) underlying these effects remains unclear. The present study evaluated the nutritional, hormonal, and morphologic effects of the STEP procedure in a rodent model of short bowel syndrome.
With institutional animal care ethics approval, Sprague-Dawley rats underwent an 80% distal bowel resection, anastomosing the 30 cm remnant of jejunum to the ascending colon; at day 14, animals were randomly assigned to control or a STEP procedure (n = 8/group). Animals were pair-fed with normal chow; after a further 3 weeks, intestinal transit, hormonal and metabolic balance studies were done, and intestinal tissues were taken for analysis.
The STEP group had increased weight gain (resected: -0.34% +/- 2.9% vs STEP: 2.5% +/- 1.5%), increased bowel length (34.1 +/- 1.5 vs 36.9 +/- 2.2 cm), increased jejunal villus height (555 +/- 59 vs 635 +/- 65 microm), decreased rates of crypt cell apoptosis, increased expression of mRNA for the GLP-2 receptor, and increased postprandial production of glucagon-like peptide 2 (45 +/- 14 vs 65 +/- 12 pmol/L) (P < .05 by Student t test). There were no differences in intestinal transit; absorption of total calories, protein, fat, or carbohydrate; crypt cell proliferation rates; or the expression of intestinal transporter proteins (SGLT-1, GLUT-2, and GLUT-5).
The STEP procedure improves weight gain and augments gross and microscopic intestinal morphology in severe experimental short bowel syndrome. Postprandial GLP-2 levels are increased, as is the expression of the GLP-2 receptor; these mechanisms may contribute to these metabolic effects and may be useful in guiding the use of the STEP procedure clinically.
背景/目的:系列横断肠成形术(STEP)在临床上似乎有益,但这些效果背后的机制仍不清楚。本研究在短肠综合征啮齿动物模型中评估了STEP手术对营养、激素和形态学的影响。
经机构动物护理伦理批准,将Sprague-Dawley大鼠的80%远端肠切除,将30 cm的空肠残端与升结肠吻合;在第14天,将动物随机分为对照组或接受STEP手术组(每组n = 8)。动物成对喂以正常食物;再过3周后,进行肠道转运、激素和代谢平衡研究,并取肠道组织进行分析。
STEP组体重增加更多(切除组:-0.34%±2.9% vs STEP组:2.5%±1.5%),肠长度增加(34.1±1.5 vs 36.9±2.2 cm),空肠绒毛高度增加(555±59 vs 635±65μm),隐窝细胞凋亡率降低,GLP-2受体mRNA表达增加,餐后胰高血糖素样肽2分泌增加(45±14 vs 65±12 pmol/L)(Student t检验,P < 0.05)。肠道转运、总热量、蛋白质、脂肪或碳水化合物的吸收、隐窝细胞增殖率或肠道转运蛋白(SGLT-1、GLUT-2和GLUT-5)的表达无差异。
STEP手术可改善严重实验性短肠综合征的体重增加,并改善肠道大体和微观形态。餐后GLP-2水平升高,GLP-2受体表达也增加;这些机制可能促成了这些代谢效应,可能有助于临床指导STEP手术的应用。