Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease.
Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease.
复制标题
大鼠醋酸结肠炎中花生四烯酸的代谢。
DOI：
10.1016/s0016-5085(85)80132-3
复制
发表时间：
1985
期刊：
影响因子：
29.4
通讯作者：
Stenson,WF
中科院分区：
文献类型：
--
作者：
Sharon,P;Stenson,WF
我们最近报道，人类炎症性肠病粘膜含有大量的白三烯B4，一种由花生四烯酸通过脂氧合酶途径形成的强效趋化剂。为了更全面地评估花生四烯酸代谢产物在肠道炎症介导中的作用，我们研究了花生四烯酸在动物模型中的代谢;大鼠乙酸结肠炎。乙酸结肠炎粘膜与花生四烯酸的孵育导致白三烯B4和一系列单羟基脂肪酸的产生，这些都是脂氧合酶途径的产物，加上少量的环氧合酶产物，包括前列腺素E2。所有这些代谢物都是由乙酸处理大鼠的粘膜产生的，其数量显著高于对照组。醋酸性结肠炎的花生四烯酸代谢模式与人类炎症性肠病的花生四烯酸代谢模式非常相似。此外，在乙酸处理的粘膜中的白三烯B4的浓度几乎与人类炎症性肠病粘膜中的浓度相同，并且是正常大鼠结肠粘膜中的浓度的50倍。这些数据表明，脂氧合酶产物，包括白三烯B4，可能是肠道炎症的重要介质，在各种各样的炎症条件。此外，在花生四烯酸代谢的人类炎症性肠病和乙酸结肠炎的相似性，可以允许使用该模型，也许其他动物模型的肠道炎症，在筛选潜在的治疗剂的炎症性肠病。
We recently reported that human inflammatory bowel disease mucosa contains large amounts of leukotriene B4, a potent chemotactic agent formed from arachidonic acid through the lipoxygenase pathway. To more fully evaluate the role of arachidonic acid metabolites in the mediation of intestinal inflammation, we studied arachidonate metabolism in an animal model; acetic acid colitis in the rat. Incubation of acetic acid colitis mucosa with arachidonic acid resulted in the production of leukotriene B4 and a series of monohydroxy fatty acids, all products of the lipoxygenase pathway, plus much smaller amounts of cyclooxygenase products including prostaglandin E2. All of these metabolities were made in significantly greater quantities by mucosa from acetic acid-treated rats than by controls. The pattern of arachidonate metabolism in acetic acid colitis was strikingly similar to that in human inflammatory bowel disease. Moreover, the concentration of leukotriene B4 in acetic acid-treated mucosa was almost identical to that in human inflammatory bowel disease mucosa and was 50 times greater than that in normal rat colonic mucosa. These data indicate that lipoxygenase products, including leukotriene B4, may be important mediators of intestinal inflammation in a wide variety of inflnmmntnrv cnnditions. Moreover, the similarities in the metabolism of arachidonate by human inflammatory bowel disease and by acetic acid colitis may allow the use of this model, and perhaps other animal models of intestinal inflammation, in the screening of potential therapeutic agents for inflammatory bowel disease.