TNS 诱导的大鼠慢性和免疫性肠炎中的花生四烯酸代谢,以及 5-ASA 的作用。
Arachidonic acid metabolism in TNS-induced chronic and immunologic enteritis in rats, and the effect of 5-ASA.
机构信息
Department of Pharmacology Erasmus University Rotterdam The Netherlands.
出版信息
Mediators Inflamm. 1993;2(5):391-5. doi: 10.1155/S0962935193000559.
Inflammation of the rat distal intestine was induced by intradermal sensitization and subsequent multiple intrajejunal challenge with the hapten 2,4,6-trinitrobenzenesulphonic acid (TNBS) via an implanted catheter. The time course of the inflammatory reaction was followed by determination of the enteritis score and measurement of in vitro eicosanoid formation of homogenates of the gut after 0, 1, 2, 4, 7, 14 and 21 days of local daily challenge with 0.08% TNBS. There was a small initial increase of eicosanoid formation, reached at days 1 and 2, followed by a significant increase in metabolism of arachidonic acid on day 21. Although at day 1 a four-fold increase in inflammation score was reached, no further significant changes were observed during the following 3 weeks. The greatest increase in metabolite formation was observed in prostanoids TxB(2), PGE(2). and PGD(2) and the 5-lipoxygenase product LTC(4), whereas minor changes were found for LTB(4) and other lipoxygenase products such as 12- and 15-HETE. The formation of these metabolites was already inhibited by low-dose 5-aminosalicylic acid (5-ASA), given orally twice daily during the 3 weeks challenge period, while the enteritis score was affected dosedependently.
通过植入的导管,用半抗原 2,4,6-三硝基苯磺酸(TNBS)对大鼠进行皮内致敏和随后的多次空肠内挑战,可诱导大鼠远端小肠炎症。通过测定肠炎评分和在局部每天接受 0.08%TNBS 挑战后 0、1、2、4、7、14 和 21 天测量肠道匀浆中体外类二十烷酸形成,来跟踪炎症反应的时间进程。在第 1 和第 2 天达到了类二十烷酸形成的小初始增加,随后在第 21 天观察到花生四烯酸代谢的显著增加。尽管在第 1 天炎症评分增加了四倍,但在接下来的 3 周内没有观察到进一步的显著变化。代谢产物形成的最大增加发生在前列腺素 TxB(2)、PGE(2)和 PGD(2)和 5-脂氧合酶产物 LTC(4),而 LTB(4)和其他脂氧合酶产物(如 12-和 15-HETE)的变化较小。在 3 周的挑战期间,每天口服两次低剂量 5-氨基水杨酸(5-ASA)给药即可抑制这些代谢产物的形成,而肠炎评分则呈剂量依赖性受到影响。