Becker P M, Sanders S P, Price P, Christman B W
The Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD, USA.
Free Radic Biol Med. 1998 Oct;25(6):703-11. doi: 10.1016/s0891-5849(98)00152-x.
Pulmonary edema develops when pulmonary blood flow is interrupted, then restored. Because the lung is not always hypoxic when ischemic, mechanisms of pulmonary ischemia-reperfusion injury are likely to differ from systemic organs, where reactive oxygen species generated during reperfusion mediate organ dysfunction. We previously showed that pulmonary vascular permeability of isolated ferret lungs increased prior to reperfusion, if ventilation was maintained while blood flow was impaired. To determine whether reactive oxygen metabolites generated during ischemia mediated ischemic injury, we measured tissue levels of F2-isoprostanes as an index of lipid peroxidation, 30 min after administration of glucose (5 mM)-glucose oxidase (GOX, 0.1 U/ml), or after short (45 min) or long (180 min) ventilated ischemia, in isolated ferret lungs. Osmotic reflection coefficient for albumin (sigma alb), an estimate of vascular protein permeability, was measured in the same lungs. Tissue F2-isoprostanes increased 375% after exposure to glucose-GOX in association with a 42% decrease in sigma alb, and administration of catalase (CAT, 100,000 U) and superoxide dismutase (SOD, 25,000 U) completely attenuated this lipid peroxidation. In contrast, tissue F2-isoprostanes increased only 60% following 45 min of ischemia, then did not increase additionally. sigma alb was not altered by 45 min of ischemia, but decreased 72% following 180 min of ischemia. CAT+SOD did not alter F2-isoprostane formation during ischemia, but partially attenuated vascular injury. These results suggest that tissue levels of F2-isoprostanes reflect lung lipid peroxidation, but that F2-isoprostane generation does not directly increase vascular permeability following ventilated pulmonary ischemia.
当肺血流中断然后恢复时，肺水肿就会发生。由于肺在缺血时并非总是缺氧，肺缺血再灌注损伤的机制可能与全身器官不同，在全身器官中，再灌注期间产生的活性氧介导器官功能障碍。我们之前发现，如果在血流受损时维持通气，分离的雪貂肺的肺血管通透性在再灌注前会增加。为了确定缺血期间产生的活性氧代谢产物是否介导缺血性损伤，我们在分离的雪貂肺中，在给予葡萄糖（5 mM）-葡萄糖氧化酶（GOX，0.1 U/ml）后30分钟，或在短时间（45分钟）或长时间（180分钟）通气缺血后，测量了作为脂质过氧化指标的F2-异前列腺素的组织水平。在同一肺中测量了白蛋白的渗透反射系数（σalb），它是血管蛋白通透性的一个指标。暴露于葡萄糖-GOX后，组织F2-异前列腺素增加了375%，同时σalb下降了42%，而给予过氧化氢酶（CAT，100,000 U）和超氧化物歧化酶（SOD，25,000 U）完全减弱了这种脂质过氧化。相比之下，缺血45分钟后组织F2-异前列腺素仅增加了60%，然后没有进一步增加。缺血45分钟时σalb没有改变，但缺血180分钟后下降了72%。CAT+SOD在缺血期间没有改变F2-异前列腺素的形成，但部分减弱了血管损伤。这些结果表明，F2-异前列腺素的组织水平反映了肺脂质过氧化，但在通气性肺缺血后，F2-异前列腺素的产生并没有直接增加血管通透性。
