Pathophysiology of disrupted intestinal mucosal barrier (increased permeability and protein loss)

1.餐后肠道内容物油酸和牛磺胆酸均能增加肠道通透性，且呈剂量依赖性。黏液凝胶抑制了由腔内因子引起的通透性增加，这种作用可能与肠粘膜屏障功能有关。肠道粘膜通透性不仅可以通过外源性一氧化氮（NO）增加，还可以通过肠上皮细胞产生的NO增加。肠上皮细胞产生趋化因子在IL-1 β或TNFalpha存在时，肠上皮细胞产生的白细胞介素(IL) -8增加。环孢素A显著降低细胞因子诱导的IL-8产生，而FK506或地塞米松没有影响。肠上皮细胞在IL-1 β或TNFalpha存在时，MCP-1和eotaxin的产生也增加。丁酸钠，一种短链脂肪酸，减少细胞因子诱导这些趋化因子的产生。炎症性肠病（IBD）患者粪便中性粒细胞衍生蛋白水平升高。Lf是这些蛋白中最适合用作临床应用的中性粒细胞来源的粪便炎症标志物。粪便α - 1抗胰蛋白酶（AT）水平的升高至少部分是由于肠道炎症患者肠上皮细胞分泌的AT增加。粪便α - 1- at的结构分析有助于评估IBD的疾病活动性。粪便中嗜酸性粒细胞颗粒衍生蛋白的测量对于监测IBD患者的疾病活动和预测复发是有用的。嗜酸性蛋白X （EPX，EDN）可能比嗜酸性阳离子蛋白（ECP）更适合作为粪便嗜酸性细胞标志物。

1.Intestinal permeabilityOleic acid and taurocholate, both post prandial intestinal contents, could increase the intestinal permeability in a dose dependent manner. The mucus gellayr inhibited the increased permeability induced by intraluminal factors, and this action may contribute to the intestinal mucosal barrier function. Intestinal mucosal permeability is also increased by not only exogenously administered nitric oxide (NO) but also by NO produced by intestinal epithelial cells.2.Chemokine production by intestinal epithelial cellThe produstion of interleukin (IL) -8 by intestinal epithelial cells was increased in the presence of IL-1 beta or TNFalpha. Cyclosporine A significantly reduced cytokine induced IL-8 production, whereas FK506 or dexamethasone had no effect. The production of MCP-1 and eotaxin were also increased by intestinal epithelial cells in the presence of IL-1 beta or TNFalpha. Sodium butyrate, a short-chain fatty acid, reduced cytokine-induced these chemokine production.3.Fecal proteins in patients with inflammatory bowel disease (IBD)The fecal levels of neutrophil-derived proteins were increased in patients with inflammatory bowel disease. Lf was the most suitable of these proteins to use as a neutrophil-derived fecal marker of inflammation for clinical application. An increase of fecal alpha1-antitrypsin (AT) level is at least partly due to an increase of its secretion from intestinal epithelial cells in patients with intestinal inflammation. The structural analysis of fecal alpha1-AT is useful for assessment of disease activity in IBD.The measurement of eosinophil granule-derived proteins in feces is useful for monitoring the disease activity and predicting relapse in patients with IBD.Eosinophil protein X (EPX,EDN) may be more suit able than eosinophil cationic protein (ECP) as a fecal eosinophil marker.