BACKGROUND Preterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations. METHODS Newborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days. RESULTS Severe hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation). CONCLUSIONS Severe but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

中文翻译：

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新生小鼠的严重但不是中度的高氧血症会在成年后导致气肿性肺表型，而不会持续存在氧化应激和炎症。

背景技术早产新生儿通常需要补充氧气，但是高氧条件也会损害早产的肺。主要在新生小鼠模型中研究氧气引起的肺部损伤，方法是使用高于75％的氧气浓度并观察短期影响。因此，我们旨在研究长期影响及其对不同氧气浓度的依赖性。方法新生小鼠暴露于中度和重度高氧空气条件下（50 vs. 75％O2）达14天，然后再经历较长时间的常氧条件。在60或120天的年龄收集与肺有关的参数。结果严重的高氧导致肺泡密度降低，实质性气隙的扩大和弹性纤维的断裂，以及更高的肺顺应性和峰值气流限制，以及对以后生活中通气介导的损伤的敏感性更高。但是，这些长期的肺部结构和功能变化并没有限制自愿的身体活动。而且，它们并没有伴随着持续的炎症过程，成年期增加的活性氧（ROS）形成或抗氧化酶（超氧化物歧化酶，过氧化氢酶）和与肺弹性相关的蛋白（弹性蛋白，表面活性剂蛋白）的表达变化。与严重的高氧相反，中度高氧对肺的损害较小，但并非没有长期影响（较高的肺顺应性，没有峰值气流限制，ROS形成增加）。结论严重但不是中度的新生儿高氧会导致肺气肿，而在成年期不会持续存在氧化应激和炎症。由于弹性纤维的现有断裂作用似乎起着关键作用，因此表明弹性蛋白保护化合物在减少长期与氧气有关的肺部损伤中的有用性。