Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure
Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure
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DOI：
10.1152/ajplung.00359.2014
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发表时间：
2015-09-01
影响因子：
4.9
通讯作者：
Sozo, Foula
中科院分区：
文献类型：
--
作者：
Bouch, Sheena;O'Reilly, Megan;Sozo, Foula
由于肺发育不成熟，早产儿通常需要补充氧气，但高氧会增加以后患呼吸系统疾病的风险。我们的目的是比较轻度和中度新生儿高氧对肺氧化应激和炎症标志物以及肺结构的影响；评估了即时效果和持续效果。新生小鼠（C57BL6/J）从出生到出生后第7天（P7d），分别在室内空气（21% O-2）、轻度（40% O-2）或中度（65% O-2）高氧环境中饲养。这些小鼠要么在P7d（即时效应）被杀死，要么在空气中生活直到成年（P56d，持续效应）。我们在P7d的肺组织中检测到巨噬细胞，在P56d的支气管肺泡灌洗液（BALF）中检测到免疫细胞。在P7d和P56d，我们评估肺氧化应激[血红素加氧酶-1 （HO-1）和硝基酪氨酸染色]和肺结构。研究人员对这些数据进行了性别差异调查。在P7d， 65% O-2组的HO-1基因表达高于21% O-2组。在P56d， 40% O-2和65% O-2组的硝基酪氨酸染色面积和免疫细胞数量均大于21% O-2组。暴露于65%的O-2，而不是40%的O-2，会导致短期内肺泡变大，组织分数降低，并持续减少细支气管-肺泡附着物。暴露于40%或65%的O-2会导致肺部氧化应激和免疫细胞持续增加，表明成人肺部存在慢性炎症。与65% O-2不同，40% O-2不影响肺结构。
Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O-2), mild (40% O-2), or moderate (65% O-2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O-2 group than in the 21% O-2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O-2 and 65% O-2 groups relative to the 21% O-2 group. Exposure to 65% O-2, but not 40% O-2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O-2 or 65% O-2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O-2, 40% O-2 does not affect lung architecture.