Kuper-Sassé Margaret E, MacFarlane Peter M, Mayer Catherine A, Martin Richard J, Prakash Y S, Pabelick Christina M, Raffay Thomas M
Department of Pediatrics, Case Western Reserve University, UH Rainbow Babies & Children's Hospital, Cleveland, OH 44106, USA.
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Children (Basel). 2021 Mar 5;8(3):195. doi: 10.3390/children8030195.
Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures.
母体感染是早产的一个风险因素。早产新生儿通常需要补充氧气来治疗新生儿呼吸窘迫。新生儿高氧暴露与气道和血管高反应性有关，而母体感染的并发症则各不相同。在一个产前母体腹腔注射脂多糖（LPS，胚胎第18天）随后新生儿高氧暴露（40%氧气×7天）的小鼠模型中，使用精确切割的活肺切片在21日龄时测量肺内气道和血管反应性。与室内空气对照组相比，高氧增加了气道对乙酰甲胆碱的反应性。产前母体LPS在室内空气中并未改变气道反应性。母体LPS和高氧联合暴露与对照组相比增加了气道反应性，尽管最大反应与单独高氧暴露相比有所减弱。血管对5-羟色胺的反应性在高氧或室内空气中没有显著差异；然而，产前母体LPS似乎减弱了室内空气中血管的反应性。在室内空气恢复后，与室内空气生理盐水对照组相比，LPS与高氧肺显示炎症和纤维化基因上调（TNFαR1、iNOS和TGFβ）。在这个模型中，轻度新生儿高氧增加气道但不增加血管反应性。产前母体LPS并未进一步增加高氧气道反应性。然而，从母体LPS和新生儿高氧暴露恢复数周后，炎症基因仍上调。
