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炎症性肠病中的肠道纤维化——一个动态的、多因素过程。

Intestinal fibrosis in IBD--a dynamic, multifactorial process.

作者信息

Rieder Florian, Fiocchi Claudio

机构信息

The Cleveland Clinic Foundation, Lerner Research Institute, Department of Pathobiology, Cleveland, OH 44195, USA.

出版信息

Nat Rev Gastroenterol Hepatol. 2009 Apr;6(4):228-35. doi: 10.1038/nrgastro.2009.31.

Abstract

Intestinal fibrosis is a common and potentially serious complication of IBD that results from the reaction of intestinal tissue to the damage inflicted by chronic inflammation. The traditional view that fibrosis is inevitable or irreversible in patients with IBD is progressively changing in light of improved understanding of the cellular and molecular mechanisms that underlie the pathogenesis of fibrosis in general, and, in particular, intestinal fibrosis. These mechanisms are complex and dynamic, and involve multiple cell types, interconnected cellular events and a large number of soluble factors. In addition, owing to a breakdown of the epithelial barrier during inflammation of the gut, luminal bacterial products induce an innate immune response, which is triggered by activation of immune and nonimmune cells alike. Comprehension of the mechanisms of intestinal fibrosis will create a conceptual and practical framework that could achieve the specific blockade of fibrogenic pathways, allow for the estimation of risk of fibrotic complications, permit the detection of early fibrotic changes and, eventually, enable the development of treatments customized to the type and stage of each patient's IBD.

摘要

肠道纤维化是炎症性肠病(IBD)常见且可能严重的并发症,它源于肠道组织对慢性炎症造成的损伤所产生的反应。鉴于对一般纤维化发病机制,尤其是肠道纤维化发病机制的细胞和分子机制有了更深入的了解,传统观点认为IBD患者的纤维化不可避免或不可逆转的观念正在逐渐改变。这些机制复杂且动态,涉及多种细胞类型、相互关联的细胞事件以及大量可溶性因子。此外,由于肠道炎症期间上皮屏障的破坏,管腔细菌产物会引发先天性免疫反应,免疫细胞和非免疫细胞的激活均可触发该反应。对肠道纤维化机制的理解将创建一个概念性和实用性框架,该框架可实现对纤维化途径的特异性阻断,有助于评估纤维化并发症的风险,能够检测早期纤维化变化,并最终促成针对每位IBD患者的类型和阶段定制治疗方案的开发。

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