| 摘要: | 發炎性腸道疾病為影響整個消化道或結腸黏膜的疾病，輔助型T細胞(helper T cell, Th)與調節型T細胞(regulatory T cell, Treg)之免疫反應失調為其致病機制之一。麩醯胺(glutamine, Gln)為具有免疫調節功能之營養素，本實驗在小鼠飲食中添加Gln，探討Gln對dextran sulfate sodium (DSS)誘發急性腸炎造成之T細胞失衡及過度發炎的影響。動物隨機分為2組正常控制組(C組及G組)及2組DSS腸炎組(DC組及DG組)，C組及DC組餵食一般組成之飼料，G組及DG組則以占飼料總氮量25%的Gln取代部份酪蛋白。連續餵食10天，第6天時，於腸炎組之飲水中添加1.5%之DSS，連續5天後於隔日犧牲。結果發現，在各測定項目中，C組與G組皆無統計差異。DC組血漿haptoglobin、腸沖洗液中免疫球蛋白(immunoglobin, Ig)G、單核球趨化蛋白(monocyte chemoattractant protein)-1和腫瘤壞死因子(tumor necrosis factor)-α濃度皆高於控制組，而DG組則低於DC組。T細胞表現方面，DG組血中表現interleukin-17F和interferon-γ之Th細胞比率及腸系膜淋巴結(mesenteric lymphatic node, MLN)中T-bet和ROR-γt之mRNA表現量低於DC組，血中Treg細胞比率及MLN中Foxp3之mRNA表現量則顯著高於DC組。此外，DG組大腸組織中熱休克蛋白(heat shock protein, Hsp)72 及抗細胞凋亡蛋白B cell lymphoma-extra large (Bcl-xL)之基因表現量皆顯著高於DC組，cleaved poly (adenosine diphosphate-ribose) polymerase之蛋白質表現量則顯著低於DC組。本實驗結果顯示，Gln介入可降低Th1/Th17及Th相關細胞激素表現，並增加Treg表現，顯示Gln可調控DSS誘發腸炎造成之Th/Treg失衡，可能進而降低發炎反應與疾病嚴重度。
Inflammatory bowel disease (IBD) is a multifactorial disorder of unknown etiology. Dysregulated immune response between T regulatory (Treg) and T-helper (Th) cells may be responsible for the pathogenic mechanism. Glutamine (Gln) is a nutrient with immune-modulatory properties. This study investigated the effects of Gln on Th/Treg cell homeostasis and colonic inflammatory mediator expression in mice with dextran sulfate sodium (DSS)-induced colitis. Mice were randomly assigned to 4 groups with 2 normal control (C & G) and 2 DSS-treated groups (DC & DG). C and DC groups were fed with a common semipurified diet, while G and DG groups received an identical diet except that part of the casein was replaced by Gln, which provided 25% of total amino acid nitrogen. The diets were fed for 10 days. At day 6, mice in the normal control groups drank distilled water and DSS groups were given distilled water containing 1.5% DSS for 5 d. At the end of the experiment, mice were sacrificed for further examination. The results showed that DSS results in higher plasma haptoglobin, colon weight/length ratio, immunoglobin G, monocyte chemoattractant protein-1, tumor necrosis factor-α levels. Gln administration lowered down the inflammatory markers in colitis. Also, the percentages of interleukin-17F, interferon-γ in blood and transcription factors T-bet, RAR-related orphan receptor-γt gene expressions in mesenteric lymphatic node were lower while blood Foxp3 was higher in the DG group than the DC group and had no differences from the C and G groups. Compared to DC group, DG group had higher heat shock protein 72 and anti-apoptotic B cell lymphoma-extra large gene expressions and lower protein levels of cleaved poly (adenosine diphosphate-ribose) polymerase in colon tissues with lower colon injury score. The results showed that Gln administration suppressed Th1/Th17 and Th-associated cytokine expressions. Also, the expression of Treg was upregulated. These findings suggest that Gln modulates the balance of Th/Treg that may consequently reduce inflammatory reaction in DSS-induced colitis. |
