Leukotriene inhibitors attenuate rat lung injury induced by hydrogen peroxide.
Leukotriene inhibitors attenuate rat lung injury induced by hydrogen peroxide.
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白三烯抑制剂可减轻过氧化氢引起的大鼠肺损伤。
DOI：
10.1164/arrd.1985.131.5.778
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Voelkel,NF
中科院分区：
文献类型：
--
作者：
Burghuber,OC;Strife,RJ;Zirrolli,J;Henson,PM;Henson,JE;Mathias,MM;Reeves,JT;Murphy,RC;Voelkel,NF
已知活性氧会引起与花生四烯酸代谢激活相关的肺损伤。由于环氧合酶途径的代谢物似乎不会介导损伤，因此我们认为 5-脂氧合酶途径可能被激活，并且抑制该途径可能会干扰损伤的发展。因此，我们试图诱导氧化性肺损伤，并通过抑制脂氧合酶途径或阻断白三烯作用来预防这种损伤。在离体大鼠肺中，将葡萄糖氧化酶添加到含葡萄糖的无细胞灌注液中，用于产生有害的氧物质。肺水肿发生并随着吸入空气中氧张力的增加而加重。肺部光学显微镜显示血管周围有液体袖带，电子显微镜显示内皮细胞损伤。肺流出物的测量结果表明，施用葡萄糖氧化酶后，5-羟基二十碳四烯酸 (5-HETE) 和环氧合酶代谢物的浓度增加； BW 755C、1160,257 和 FPL 55712 抑制葡萄糖氧化酶诱导的肺水肿。 U60,257 还抑制葡萄糖氧化酶诱导的 5-HETE 增加，而不同时抑制环氧合酶代谢物。因此，葡萄糖氧化酶通过产生活性氧刺激肺5-脂氧合酶途径，并且5-脂氧合酶抑制剂可防止氧化性肺损伤。此外，在这些实验中，损伤发生在没有循环血细胞的情况下，并且通过增加吸入氧浓度而加剧。
It is known that reactive oxygen species cause lung injury in association with activation of arachidonate metabolism. Because metabolites of the cyclooxygenase pathway do not appear to mediate the injury, we considered that the 5-lipoxygenase pathway might be activated and that inhibition of the pathway could interfere with the development of the injury. Thus, we sought to induce an oxidant lung injury and to prevent such injury by inhibiting lipoxygenase pathway or by blocking leukotriene action. In isolated rat lungs, glucose oxidase added to a glucose-containing, cell-free perfusate was used to produce the injurious oxygen species. Lung edema occurred and increased with increasing oxygen tension in the inspired air. Light microscopy of the lung showed perivascular fluid cuffs, and electron microscopy showed endothelial cell damage. Measurements in the lung effluent showed that concentrations of 5-hydroxyeicosatetraenoic acid (5-HETE) and of cyclooxygenase metabolites increased after glucose oxidase administration; BW 755C, 1160,257, and FPL 55712 inhibited the glucose-oxidase-induced lung edema. And U60,257 also inhibited the glucose-oxidase-induced increase in 5-HETE without concomitant inhibition of cyclooxygenase metabolites. Thus, glucose oxidase via generation of active oxygen species stimulated the lung 5-lipoxygenase pathway, and inhibitors of 5-lipoxygenase protected against the oxidant lung injury. Further, in these experiments, the injury occurred in the absence of circulating blood cells and was augmented by increasing the inspired oxygen concentration.