Tian Junqiang, Hao Li, Chandra Prakash, Jones Dean P, Willams Ifor R, Gewirtz Andrew T, Ziegler Thomas R
Department of Medicine, Emory University, Atlanta, GA 30322, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G348-55. doi: 10.1152/ajpgi.90233.2008. Epub 2008 Dec 18.
Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.
短肠综合征(SBS)与肠道屏障功能障碍有关。我们在SBS大鼠模型中研究了膳食谷氨酰胺(GLN)或口服抗生素(ABX)对肠道屏障功能指标的影响。成年大鼠接受60%远端小肠+近端结肠切除术(RX)或肠横断术(TX;对照)。术后20天,大鼠成对喂食含或不含L-GLN的饲料。一些接受RX且喂食对照饲料的大鼠给予口服ABX(新霉素、甲硝唑和多粘菌素B)。连续测量粪便分泌型免疫球蛋白A(sIgA)。在第21天,培养肠系膜淋巴结(MLN)中的革兰氏阴性菌。测定空肠中IgA阳性浆细胞、粪便中鞭毛蛋白和脂多糖(LPS)特异性sIgA水平以及血清总IgG、抗鞭毛蛋白IgG和抗LPS IgG水平。RX导致革兰氏阴性菌易位至MLN,血清总IgG和抗LPS IgG增加,粪便总sIgA增加。RX后,膳食GLN倾向于抑制细菌易位至MLN(-29%,P=无显著性差异),并显著降低血清中抗LPS IgG水平,增加粪便和空肠黏膜sIgA,增加粪便抗LPS特异性IgA。口服ABX消除了RX诱导的细菌易位,显著降低血清中总IgG和抗LPS IgG水平,显著降低粪便总IgA并增加粪便LPS特异性IgA。大鼠部分小肠-结肠切除与肠道革兰氏阴性菌易位以及对LPS的适应性免疫反应相关。肠道屏障功能障碍的这些指标分别通过给予膳食GLN或口服ABX得到改善或抑制。在该模型中,膳食GLN上调小肠sIgA。