Kiristioglu I, Teitelbaum D H
Department of Surgery, The University of Michigan Medical School and C. S. Mott Children's Hospital, Ann Arbor, Michigan, USA.
J Surg Res. 1998 Oct;79(2):91-6. doi: 10.1006/jsre.1998.5408.
Total parenteral nutrition (TPN) may cause increased rates of bacterial translocation (BT), possibly due to a loss of epithelial integrity. Cultured epithelial cells have been shown to lose tight junction integrity with interferon gamma (INF-gamma) an action which may be blocked by transforming growth factor beta (TGF-beta). Because intraepithelial lymphocytes (IEL) are a rich source of these cytokines in the epithelium, we hypothesized that changes in the IEL, while mice were receiving TPN, may be responsible for the mediation of such cytokine responses. C57BL/6 mice were randomized to a Control group which received intravenous saline and mouse chow, or a TPN group which received intravenous TPN with no oral feeding. At 7 days mice were assessed for BT. Isolated IEL were stained for CD4, CD8, and CD44 (as a marker for memory T-cells) and flow cytometry was performed. mRNA was extracted from remaining IEL for cytokine expression. Reverse transcriptase polymerase chain reaction was performed to detect TGF-beta1 and INF-gamma mRNA expression. Densities were standardized to beta-actin expression. The incidence of BT to mesenteric lymph nodes was 40 and 12.5%, for the TPN and Control groups, respectively. TPN led to statistically significant decreases in the CD4+, CD8-; CD4+, CD8+; and the CD8+, CD44+ IEL subpopulations (P < 0.05). mRNA expression for INF-gamma was increased by 53% (P < 0.05), and TGF-beta1 mRNA expression was decreased by 75% (P = 0.1) in the IEL of TPN mice when compared with Controls. TPN led to significant changes in the IEL. Such alterations of the IEL phenotype and function may be a critical mechanism by which epithelial integrity is lost.
全胃肠外营养（TPN）可能会导致细菌移位（BT）率增加，这可能是由于上皮完整性丧失所致。培养的上皮细胞已被证明会因γ干扰素（INF-γ）而丧失紧密连接的完整性，而转化生长因子β（TGF-β）可能会阻断这一作用。由于上皮内淋巴细胞（IEL）是上皮中这些细胞因子的丰富来源，我们推测在小鼠接受TPN期间，IEL的变化可能是介导此类细胞因子反应的原因。将C57BL/6小鼠随机分为对照组和TPN组，对照组接受静脉注射生理盐水和鼠粮，TPN组接受静脉注射TPN且不进行口服喂养。7天后评估小鼠的细菌移位情况。对分离出的IEL进行CD4、CD8和CD44（作为记忆T细胞的标志物）染色，并进行流式细胞术检测。从剩余的IEL中提取mRNA用于细胞因子表达分析。进行逆转录聚合酶链反应以检测TGF-β1和INF-γ mRNA的表达。将密度标准化为β-肌动蛋白的表达。TPN组和对照组肠系膜淋巴结的细菌移位发生率分别为40%和12.5%。TPN导致CD4 +、CD8 -；CD4 +、CD8 +；以及CD8 +、CD44 + IEL亚群出现统计学显著下降（P < 0.05）。与对照组相比，TPN小鼠的IEL中INF-γ的mRNA表达增加了53%（P < 0.05），而TGF-β1的mRNA表达下降了75%（P = 0.1）。TPN导致IEL发生显著变化。IEL表型和功能的这种改变可能是上皮完整性丧失的关键机制。
