Schmidt Reinhold, Schäfer Christoph, Luboeinski Thomas, Löckinger Alexander, Hermle Gerd, Grimminger Friedrich, Seeger Werner, Ghofrani Ardeschir, Schütte Hartwig, Günther Andreas
Medizinische Klinik II, Zentrum für Innere Medizin, Justus-Liebig-University, Giessen, Germany.
Free Radic Biol Med. 2004 Jan 1;36(1):78-89. doi: 10.1016/j.freeradbiomed.2003.10.023.
Increases in free radicals are believed to play a central role in the development of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage and deterioration of pulmonary surfactant. Continued ventilation during ischemia offers significant protection against I-R injury, but the impact of alveolar oxygen supply both on lung injury and on radical generation is still unclear. We investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation during ischemia on alveolar antioxidant status and surfactant properties in isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with controls, biophysical and biochemical surfactant properties were not altered in anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E), retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O-alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a significant increase in antioxidant compounds under anoxic and hyperoxic ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated ischemia compared with native controls (1.3 +/- 0.2 microM), but did not significantly change under anoxic and hyperoxic ventilation alone. In parallel, under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h: 0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02 microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/- 15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic ventilation. This is paralleled by an increase rather than a decrease in alveolar antioxidant levels, suggested to reflect an adaptive response to oxidative stress during ischemia.
自由基的增加被认为在肺缺血/再灌注（I-R）损伤的发展中起核心作用，导致微血管渗漏和肺表面活性物质的恶化。缺血期间持续通气可显著保护免受I-R损伤，但肺泡氧供应对肺损伤和自由基生成的影响仍不清楚。我们研究了缺血期间高氧（95% O2）和无氧（0% O2）通气对离体兔肺肺泡抗氧化状态和表面活性物质特性的影响。常氧和高氧通气、缓冲灌注肺（n = 5或6）和天然肺（n = 6）作为对照。与对照组相比，无氧和高氧通气的缺血（2、3和4小时）肺的生物物理和生化表面活性物质特性未改变。对支气管肺泡灌洗液（BALF）中几种抗氧化剂（还原型谷胱甘肽（GSH）、α-生育酚（维生素E）、视黄醇（维生素A）、抗坏血酸（维生素C）、尿酸和缩醛磷脂（1-O-烯基-2-酰基磷脂））的评估显示，在无氧和高氧通气下抗氧化化合物显著增加，在缺血3小时后达到最高水平。例如，与天然对照（1.3 +/- 0.2 microM）相比，无氧通气缺血3小时后GSH增加到5.1 +/- 0.8 microM（平均值 +/- 标准误，p <.001），高氧通气缺血后增加到2.7 +/- 0.2 microM（p <.01），但在单独的无氧和高氧通气下没有显著变化。同时，在缺血条件下，与天然对照（0.22 +/- 0.02 microM）相比，高氧（3小时：0.81 +/- 0.04 microM，p <.001）期间氧化型谷胱甘肽（GSSG）增加，但无氧（3小时：0.31 +/- 0.04 microM）通气期间保持不变，而与天然对照（16 +/- 4 pM）相比，高氧（3小时：63 +/- 15 pM，p <.01）和无氧（3小时：50 +/- 9 pM，p <.01）通气下F2-异前列腺素均升高。我们得出结论，在缺血期间，无论是无氧还是高氧通气，肺泡内衬层的氧化应激都会增加。与此同时，肺泡抗氧化水平增加而非降低，这表明反映了缺血期间对氧化应激的适应性反应。
