Kruidenier L, Verspaget H W
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Aliment Pharmacol Ther. 2002 Dec;16(12):1997-2015. doi: 10.1046/j.1365-2036.2002.01378.x.
Virtually all inflammatory mediators investigated to date seem to be dysregulated in the inflamed intestinal mucosa of patients with inflammatory bowel disease. However, which of these are actually involved in the initiation and perpetuation of intestinal tissue damage is still not fully understood. Amongst these mediators are the reactive oxygen metabolites, produced in large amounts by the massively infiltrating leucocytes. These reactive oxygen metabolites are believed to constitute a major tissue-destructive force and may contribute significantly to the pathogenesis of inflammatory bowel disease. This paper provides a concise overview of reactive oxygen metabolite biochemistry, the types of cell and tissue damage potentially inflicted by them, and the endogenous antioxidants which should prevent these harmful effects. An up-to-date summary of the available human experimental data suggests that reactive oxygen metabolite-mediated injury is important in both the primary and downstream secondary pathophysiological mechanisms underlying intestinal inflammation. Nonetheless, how the individual components of the mucosal antioxidant enzymatic cascade respond to inflammatory conditions is a neglected area of research. This particular aspect of intestinal mucosal oxidative stress therefore merits further study, in order to provide a sound, scientific basis for the design of antioxidant-directed treatment strategies for inflammatory bowel disease patients.
几乎所有迄今为止研究过的炎症介质在炎症性肠病患者发炎的肠黏膜中似乎都失调了。然而，其中哪些实际上参与了肠道组织损伤的起始和持续过程仍未完全明确。在这些介质中，有大量大量浸润的白细胞产生的活性氧代谢产物。这些活性氧代谢产物被认为是一种主要的组织破坏力，可能在很大程度上促成了炎症性肠病的发病机制。本文简要概述了活性氧代谢产物的生物化学、它们可能造成的细胞和组织损伤类型，以及应能预防这些有害影响的内源性抗氧化剂。现有人类实验数据的最新总结表明，活性氧代谢产物介导的损伤在肠道炎症的原发性和下游继发性病理生理机制中都很重要。尽管如此，黏膜抗氧化酶级联反应的各个组成部分如何应对炎症状态仍是一个被忽视的研究领域。因此，肠道黏膜氧化应激的这一特定方面值得进一步研究，以便为设计针对炎症性肠病患者的抗氧化治疗策略提供坚实的科学依据。
