Johnson K J, Fantone J C, Kaplan J, Ward P A
J Clin Invest. 1981 Apr;67(4):983-93. doi: 10.1172/jci110149.
The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.
向大鼠肺内灌注能产生氧代谢产物的酶会导致急性肺损伤。注射黄嘌呤氧化酶和黄嘌呤会引发急性肺损伤，在超氧化物歧化酶存在的情况下，但过氧化氢酶存在时则不会，这种损伤会显著减轻，这表明超氧阴离子（O₂⁻）有损伤肺的能力。灌注过氧化氢（H₂O₂）生成剂，即葡萄糖氧化酶，若剂量足够，会产生不依赖中性粒细胞的急性损伤。单独使用低剂量的葡萄糖氧化酶或单独使用乳过氧化物酶时，几乎不会发生肺损伤。然而，同时灌注这两种酶会产生严重的急性损伤，过氧化氢酶能以剂量依赖的方式阻断这种损伤，而超氧化物歧化酶则不能。在肺损伤模型中，纯化的人白细胞髓过氧化物酶而非辣根过氧化物酶可替代乳过氧化物酶。这些酶对肺的损伤作用不能归因于污染的蛋白酶的存在。灌注葡萄糖氧化酶和乳过氧化物酶所产生的急性肺损伤会进展为间质纤维化。这些研究代表了将氧代谢产物生成剂直接应用于体内诱导肺损伤。数据表明大鼠肺对多种氧代谢产物敏感，包括超氧阴离子（O₂⁻）、过氧化氢（H₂O₂）及其由乳过氧化物酶或髓过氧化物酶产生的衍生物。研究还表明，氧代谢产物所致的肺损伤可导致间质性肺纤维化。
