Guzy Claudia, Schirbel Anja, Paclik Daniela, Wiedenmann Bertram, Dignass Axel, Sturm Andreas
Department of Medicine, Division of Gastroenterology and Hepatology Charité, Universitätsmedizin Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353, Berlin, Germany.
Eur J Nutr. 2009 Feb;48(1):12-21. doi: 10.1007/s00394-008-0754-3. Epub 2008 Nov 8.
Nutritional support is an established element of therapy for various indications. However, its impact on the mucosal barrier function is not well understood.
We investigated the influence of EN and PN on intestinal epithelial cells and peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC), all of which are involved in the mucosal defense against bacterial translocation and systemic inflammation.
Integrity of epithelial cells was measured as transepithelial electrical resistance (TER) of confluent Caco-2 monolayers in the presence of 1% EN, PN and a parenteral amino acid mixture (AM). To determine wound healing capacities, an established migration model with IEC-6 cells was used. Furthermore, we investigated apoptosis, cell activation, proliferation and cytokine secretion of Caco-2, HT29 and of stimulated PBMC and LPMC cultured with or without 1 and 5% EN, AM or PN.
We demonstrated that EN, AM and PN promoted the integrity of the epithelial monolayer and reconstituted epithelial cell continuity TGF-beta-dependently and -independently. Interestingly, only PN induced apoptosis and decreased the mitochondrial membrane potential. The activation status of PBMC was significantly reduced by EN and AM. Specifically, EN leads to an increased apoptosis rate, inhibited cell cycle progression and increased pro-inflammatory cytokine secretion. Both EN and PN reduced the activation status and the release of pro- and anti-inflammatory cytokines.
Our study provides evidence that by promoting wound healing and regulating T cell function, EN, AM, and PN potently interact with the intestinal barrier and immune system, thus justifying its use in diseases accompanied by impaired mucosal barrier function.
营养支持是针对各种适应症的既定治疗要素。然而，其对黏膜屏障功能的影响尚未得到充分理解。
我们研究了肠内营养（EN）和肠外营养（PN）对肠上皮细胞、外周血（PBMC）和固有层单核细胞（LPMC）的影响，所有这些细胞都参与了抵御细菌移位和全身炎症的黏膜防御。
在存在1%的EN、PN和一种肠外氨基酸混合物（AM）的情况下，将汇合的Caco-2单层细胞的跨上皮电阻（TER）作为上皮细胞完整性的指标进行测量。为了确定伤口愈合能力，使用了已建立的IEC-6细胞迁移模型。此外，我们研究了在有或没有1%和5%的EN、AM或PN培养的情况下，Caco-2、HT29以及受刺激的PBMC和LPMC的凋亡、细胞活化、增殖和细胞因子分泌情况。
我们证明，EN、AM和PN促进了上皮单层的完整性，并通过依赖和不依赖转化生长因子-β（TGF-β）的方式重建了上皮细胞的连续性。有趣的是，只有PN诱导了凋亡并降低了线粒体膜电位。EN和AM显著降低了PBMC的活化状态。具体而言，EN导致凋亡率增加，抑制细胞周期进程，并增加促炎细胞因子的分泌。EN和PN都降低了活化状态以及促炎和抗炎细胞因子的释放。
我们的研究提供了证据，表明通过促进伤口愈合和调节T细胞功能，EN、AM和PN与肠道屏障和免疫系统有强大相互作用，因此证明了其在伴有黏膜屏障功能受损疾病中的应用合理性。
