Deficits in lung alveolarization and function after systemic maternal inflammation and neonatal hyperoxia exposure
Deficits in lung alveolarization and function after systemic maternal inflammation and neonatal hyperoxia exposure
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DOI：
10.1152/japplphysiol.01392.2009
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发表时间：
2010-05-01
影响因子：
3.3
通讯作者：
Welty, Stephen E.
中科院分区：
文献类型：
--
作者：
Velten, Markus;Heyob, Kathryn M.;Welty, Stephen E.
韦尔滕M，海欧布KM，罗杰斯LK，韦尔蒂SE.全身性母体炎症和新生儿高氧暴露后肺泡化和功能缺陷。J Appl Physiol 108：1347-1356，2010.首次发表于2010年3月11日; doi：10.1152/japplphysiol.01392.2009.-全身性母体炎症导致早产，并与支气管肺发育不良（BPD）的发展有关。患有BPD的婴儿表现为肺泡化减少、弥漫性间质纤维化伴肺泡间隔增厚和肺功能受损。我们测试了这样一个假设，即妊娠小鼠出生后高氧暴露后全身性产前LPS给药与肺结构和功能在返回室内空气（RA）后的长期改变相关，这种改变比单独高氧暴露更严重。定时妊娠的C3 H/HeN小鼠在妊娠第16天给予LPS（80 μ g/kg）或盐水。新生幼鼠暴露于RA或85%O-2 14天，然后再暴露于RA 14天。在出生后第14天和第28天收集数据并进行分析。产前LPS和出生后高氧暴露的组合产生的表型具有更多的炎症（测量为每高倍视野的巨噬细胞数），比单独在第28天的损伤。合并暴露与弥漫性纤维化反应相关[测量为羟脯氨酸含量（μ g）]，但与单独高氧相比，未诱导更严重的发育停滞。肺功能测试表明，高氧，独立于母体暴露，诱导的依从性下降，在第14天，RA恢复后并不持续。单独或联合给药在第14天诱导了耐药性增加，但仅在接受联合给药的幼仔中，耐药性增加持续到第28天。总之，全身性母体炎症和新生儿高氧的组合诱导了长时间的肺泡化停滞、弥漫性纤维化和肺力学受损的表型，这与人类BPD相似。这种新的模型应该是有用的，在设计研究的具体机制和干预措施，最终可以用来确定治疗，以防止早产儿BPD。
Velten M, Heyob KM, Rogers LK, Welty SE. Deficits in lung alveolarization and function after systemic maternal inflammation and neonatal hyperoxia exposure. J Appl Physiol 108: 1347-1356, 2010. First published March 11, 2010; doi:10.1152/japplphysiol.01392.2009.-Systemic maternal inflammation contributes to preterm birth and is associated with development of bronchopulmonary dysplasia (BPD). Infants with BPD exhibit decreased alveolarization, diffuse interstitial fibrosis with thickened alveolar septa, and impaired pulmonary function. We tested the hypothesis that systemic prenatal LPS administration to pregnant mice followed by postnatal hyperoxia exposure is associated with prolonged alterations in pulmonary structure and function after return to room air (RA) that are more severe than hyperoxia exposure alone. Timed-pregnant C3H/HeN mice were dosed with LPS (80 mu g/kg) or saline on gestation day 16. Newborn pups were exposed to RA or 85% O-2 for 14 days and then to RA for an additional 14 days. Data were collected and analyzed on postnatal days 14 and 28. The combination of prenatal LPS and postnatal hyperoxia exposure generated a phenotype with more inflammation (measured as no. of macrophages per highpower field) than either insult alone at day 28. The combined exposures were associated with a diffuse fibrotic response [measured as hydroxyproline content (mu g)] but did not induce a more severe developmental arrest than hyperoxia alone. Pulmonary function tests indicated that hyperoxia, independent of maternal exposure, induced compliance decreases on day 14 that did not persist after RA recovery. Either treatment alone or combined induced an increase in resistance on day 14, but the increase persisted on day 28 only in pups receiving the combined treatment. In conclusion, the combination of systemic maternal inflammation and neonatal hyperoxia induced a prolonged phenotype of arrested alveolarization, diffuse fibrosis, and impaired lung mechanics that mimics human BPD. This new model should be useful in designing studies of specific mechanisms and interventions that could ultimately be utilized to define therapies to prevent BPD in premature infants.