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

肠粘膜屏障破坏的病理生理学（渗透性增加和蛋白质损失）

基本信息

批准号：
07670630
负责人：
SAITOH Osamu
金额：
$ 1.41万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670630/
关键词：
intestinal mucosa intestinal epithelial cell permeability cytokine chemokine nitric oxide protein-loss endotoxin interleukin-8

项目摘要

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.

1.肠通透性：油酸和牛磺胆酸均能增加肠通透性，且呈剂量依赖性。粘液明胶可抑制肠内因素引起的通透性增加，这种作用可能与肠粘膜屏障功能有关。肠粘膜通透性增加不仅是由于外源性一氧化氮（NO）的作用，也是由于肠上皮细胞产生的NO的作用。2.肠上皮细胞产生的趋化因子在IL-1 β或TNF α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FK 506或地塞米松没有影响。在IL-1 β或TNF α存在的情况下，肠上皮细胞的MCP-1和嗜酸性粒细胞趋化因子的产生也增加。丁酸钠，一种短链脂肪酸，减少了精氨酸诱导的这些趋化因子的产生。3.炎症性肠病（IBD）患者粪便中的蛋白质炎症性肠病患者粪便中嗜中性粒细胞衍生的蛋白质水平增加。Lf是这些蛋白质中最适合用作临床应用的嗜中性粒细胞来源的炎症粪便标记物。粪便α 1-抗胰蛋白酶（AT）水平的增加至少部分是由于肠道炎症患者肠上皮细胞分泌AT的增加。粪便中α 1-AT的结构分析有助于IBD病情活动性的评估，粪便中嗜酸性粒细胞颗粒衍生蛋白的检测有助于IBD病情活动性的监测和复发的预测，嗜酸性粒细胞蛋白X（EPX，EDN）可能比嗜酸性粒细胞阳离子蛋白（ECP）更适合作为IBD患者粪便中嗜酸性粒细胞的标志物。