Van Assche Gert, Geboes Karel, Rutgeerts Paul
Division of Gastroenterology, Leuven University Hospital, Herestraat 49, 3000 Leuven, Belgium.
Inflamm Bowel Dis. 2004 Jan;10(1):55-60. doi: 10.1097/00054725-200401000-00009.
Intestinal fibrostenosis is a frequent and debilitating complication of Crohn's disease (CD), not only resulting in small bowel obstruction, but eventually in repeated bowel resection and short bowel syndrome. Over one third of patients with CD have a clear stenosing disease phenotype, often in the absence of luminal inflammatory symptoms. Intestinal fibrosis is a consequence of chronic transmural inflammation in CD. As in other organs and tissues, phenotypic transformation and activation of resident mesenchymal cells, such as fibroblasts and smooth muscle cells, underlie fibrogenesis in the gut. The molecular mechanisms and growth factors involved in this process have not been identified. However, it is clear that inflammatory mediators may have effects on mesenchymal cells in the submucosa and the muscle layers that are profoundly different from their action on leukocytes or epithelial cells. Transforming growth factor-beta (TGF-beta), for instance, has profound anti-inflammatory activity in the mucosa and probably serves to keep physiologic inflammation at bay, but at the same time it appears to be driving the process of fibrosis in the deeper layers of the gut. Tumor necrosis factor, on the other hand, has antifibrotic bioactivity and pharmacologic inhibition of this cytokine carries a theoretical risk of enhanced stricture formation. Endoscopic management of intestinal strictures with balloon dilation is an accepted strategy to prevent or postpone repeated surgery, but careful patient selection is of paramount importance to ensure favorable long-term outcomes. Specific medical therapy aimed at preventing or reversing intestinal fibrosis is not yet available, but candidate molecules are emerging from research in the liver and in other organs.
肠道纤维狭窄是克罗恩病（CD）常见且使人虚弱的并发症，不仅会导致小肠梗阻，最终还会引发反复肠道切除和短肠综合征。超过三分之一的CD患者具有明确的狭窄性疾病表型，通常无腔内炎症症状。肠道纤维化是CD慢性透壁性炎症的结果。与其他器官和组织一样，肠道纤维化的发生机制是成纤维细胞和平滑肌细胞等常驻间充质细胞的表型转化和激活。该过程涉及的分子机制和生长因子尚未明确。然而，很明显炎症介质对黏膜下层和肌层间充质细胞的作用可能与它们对白细胞或上皮细胞的作用截然不同。例如，转化生长因子-β（TGF-β）在黏膜中具有显著的抗炎活性，可能有助于抑制生理性炎症，但同时它似乎也在推动肠道深层的纤维化进程。另一方面，肿瘤坏死因子具有抗纤维化生物活性，对该细胞因子的药物抑制在理论上存在增加狭窄形成的风险。采用球囊扩张术对肠道狭窄进行内镜治疗是预防或推迟反复手术的一种公认策略，但谨慎选择患者对于确保良好的长期疗效至关重要。目前尚无旨在预防或逆转肠道纤维化的特异性药物治疗方法，但肝脏及其他器官的研究正在涌现出一些候选分子。
