Background Supplemental oxygen exposure administered to premature infants is associated with chronic lung disease and abnormal pulmonary function. This study used mild (40%), moderate (60%), and severe (80%) oxygen to determine how hyperoxia-induced changes in lung structure impact pulmonary mechanics in mice. Methods C57BL/6J mice were exposed to room air or hyperoxia from birth through postnatal day 8. Baseline pulmonary function and methacholine challenge was assessed at 4 and 8 weeks of age, accompanied by immunohistochemical assessments of both airway (smooth muscle, tethering) and alveolar (simplification, elastin deposition) structure. Results Mild/moderate hyperoxia increased baseline airway resistance (40% only) and airway hyperreactivity (40 and 60%) at 4 weeks accompanied by increased airway smooth muscle deposition, which resolved at 8 weeks. Severe hyperoxia increased baseline compliance, baseline resistance, and total elastin/surface area ratio without increasing airway hyperreactivity, and was accompanied by increased alveolar simplification, decreased airway tethering, and changes in elastin distribution at both time points. Conclusions Mild to moderate hyperoxia causes changes in airway function and airway hyperreactivity with minimal parenchymal response. Severe hyperoxia drives its functional changes through alveolar simplification, airway tethering, and elastin redistribution. These differential responses can be leveraged to further develop hyperoxia mouse models.

中文翻译：

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小鼠新生儿高氧后的肺力学和结构性肺发育

背景 对早产儿进行补充氧气暴露与慢性肺病和肺功能异常有关。本研究使用轻度 (40%)、中度 (60%) 和重度 (80%) 氧气来确定高氧诱导的肺结构变化如何影响小鼠的肺力学。方法 C57BL/6J 小鼠从出生到出生后第 8 天都暴露在室内空气或高氧环境中。 在 4 和 8 周龄时评估基线肺功能和乙酰甲胆碱激发，同时对气道（平滑肌、束缚）和肺泡进行免疫组织化学评估（简化，弹性蛋白沉积）结构。结果 轻度/中度高氧在 4 周时增加了基线气道阻力（仅 40%）和气道高反应性（40% 和 60%），伴随气道平滑肌沉积增加，8周就解决了。严重的高氧增加了基线顺应性、基线阻力和总弹性蛋白/表面积比，但不增加气道高反应性，并伴随着肺泡简化增加、气道束缚减少以及两个时间点弹性蛋白分布的变化。结论 轻度至中度高氧导致气道功能和气道高反应性的变化，而实质反应极小。严重的高氧通过肺泡简化、气道束缚和弹性蛋白重新分布来驱动其功能变化。这些差异反应可用于进一步开发高氧小鼠模型。并且伴随着两个时间点的肺泡简化增加、气道束缚减少以及弹性蛋白分布的变化。结论 轻度至中度高氧导致气道功能和气道高反应性的变化，而实质反应极小。严重的高氧通过肺泡简化、气道束缚和弹性蛋白重新分布来驱动其功能变化。这些差异反应可用于进一步开发高氧小鼠模型。并且伴随着两个时间点的肺泡简化增加、气道束缚减少以及弹性蛋白分布的变化。结论 轻度至中度高氧导致气道功能和气道高反应性的变化，而实质反应极小。严重的高氧通过肺泡简化、气道束缚和弹性蛋白重新分布来驱动其功能变化。这些差异反应可用于进一步开发高氧小鼠模型。和弹性蛋白重新分布。这些差异反应可用于进一步开发高氧小鼠模型。和弹性蛋白重新分布。这些差异反应可用于进一步开发高氧小鼠模型。