OXYGEN RADICALS IN ULCERATIVE-COLITIS
OXYGEN RADICALS IN ULCERATIVE-COLITIS
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DOI：
10.1016/0891-5849(92)90079-v
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发表时间：
1992-08-01
影响因子：
7.4
通讯作者：
BABBS, CF
中科院分区：
文献类型：
--
作者：
BABBS, CF
本文综述了病理生理学概念，超氧化物和过氧化氢，产生的激活白细胞，连同低分子量螯合铁来自粪便来源和变性血红蛋白，放大炎症反应和随后的粘膜损伤患者的活动性发作溃疡性结肠炎。其致病机制主要有：（1）铁的吸收有限，铁在粪便中富集; (2)溃疡性结肠炎的特征性粘膜出血，以及慢性贫血的补充口服铁剂治疗，进一步共同维持或升高结肠炎粘膜铁浓度。(3)芬顿化学，特别是由白细胞产生的超氧化物和过氧化氢驱动，导致羟基自由基的形成。(4)由此产生的氧化应激导致隐窝扩张和繁殖，通过脂质过氧化直接破坏膜或通过产生二次毒性氧化剂如氯胺。(5)脂质过氧化的趋化产物，包括4-羟基壬烯醛，提供正反馈以加速这种炎症/氧化过程，导致疾病的急性加重。(6)其他氧化产物，如氧化色氨酸代谢物，由粘膜中或粘膜附近的自由基机制产生，可能作为致癌物或肿瘤促进剂，导致慢性溃疡性结肠炎患者结肠癌的发病率极高。通过这种方式，氧化剂形成的自我维持循环可能会放大溃疡性结肠炎中炎症和粘膜损伤的爆发。这一概念，如果被随后的研究证明是正确的，将为溃疡性结肠炎的管理提供几种新的临床方法，包括使用SOD模拟物，铁螯合剂和断链抗氧化剂。
This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.