Peskar B M
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, FRG.
J Physiol Pharmacol. 1991 Jun;42(2):135-45.
Exposure of the rat gastric mucosa to ethanol stimulates the generation of leukotriene (LTC4) and 15-hydroxyeicosatetraenoic acid, but not of thromboxanes and prostaglandins. Lipoxygenase activation is not found with other topical irritants or nonsteroidal anti-inflammatory drugs. A number of gastroprotective drugs dose-dependently inhibit the stimulatory action of ethanol on mucosal LTC4 formation closely parallel to their protective activity suggesting that ethanol-induced damage and activation of lipoxygenases may involve common targets which are simultaneously counteracted by certain types of protective agents. Selective inhibition of 5-lipoxygenase, however, does not confer protection against gastric mucosal damage caused by topical irritants or non-steroidal anti-inflammatory drugs. Thus, although leukotrienes may mediate certain reactions elicited by gastric ulcerogens such as submucosal venular constriction and mucosal microvascular engorgement, they do not appear to be major mediators of ulcerogen-induced tissue necrosis. The contribution of other products of the various pathways of arachidonic acid metabolism to gastric mucosal injury and the mechanism underlying the close interrelationship between protection and inhibition of LTC4 formation observed with certain compounds remains to be investigated.
大鼠胃黏膜暴露于乙醇会刺激白三烯（LTC4）和15-羟基二十碳四烯酸的生成，但不会刺激血栓素和前列腺素的生成。其他局部刺激物或非甾体抗炎药不会激活脂氧合酶。许多胃保护药物剂量依赖性地抑制乙醇对黏膜LTC4形成的刺激作用，这与其保护活性密切平行，表明乙醇诱导的损伤和脂氧合酶的激活可能涉及共同靶点，某些类型的保护剂可同时对其产生拮抗作用。然而，选择性抑制5-脂氧合酶并不能预防局部刺激物或非甾体抗炎药引起的胃黏膜损伤。因此，尽管白三烯可能介导胃溃疡原引发的某些反应，如黏膜下小静脉收缩和黏膜微血管充血，但它们似乎不是溃疡原诱导的组织坏死的主要介质。花生四烯酸代谢的各种途径的其他产物对胃黏膜损伤的作用以及某些化合物观察到的保护作用与抑制LTC4形成之间密切相互关系的潜在机制仍有待研究。
