Department of Pediatrics, Division of Neonatology and Developmental Biology, David Geffen School of Medicine, Neonatal Research Center, University of California, Los Angeles, California.
Pediatr Res. 2014 Mar;75(3):395-402. doi: 10.1038/pr.2013.233. Epub 2013 Dec 6.
Caffeine is a nonspecific adenosine receptor antagonist used in premature neonates to treat apnea of prematurity. While its use may reduce the incidence of bronchopulmonary dysplasia (BPD), the precise mechanisms remain unknown. Evidence of increased adenosine levels are noted in chronic lung diseases including tracheal aspirates of infants with BPD. Utilizing a well-characterized newborn mouse model of alveolar hypoplasia, we hypothesized that hyperoxia-induced alveolar inflammation and hypoplasia is associated with alterations in the adenosine signaling pathway.
Newborn murine pups were exposed to a 14-d period of hyperoxia and daily caffeine administration followed by a 14-d recovery period in room air. Lungs were collected at both time points for bronchoalveolar lavage (BAL) analysis as well as histopathology and mRNA and protein expression.
Caffeine treatment increased inflammation and worsened alveolar hypoplasia in hyperoxia-exposed newborn mice. These changes were associated with decreased alveolar type II (ATII) cell numbers, increased cell apoptosis, and decreased expression of A2A receptors. Following discontinuation of caffeine and hyperoxia, lung histology returned to baseline levels comparable to hyperoxia exposure alone.
Results of this study suggest a potentially adverse role of caffeine on alveolar development in a murine model of hyperoxia-induced alveolar hypoplasia.
咖啡因是一种非特异性腺苷受体拮抗剂，用于治疗早产儿呼吸暂停。虽然它的使用可能会降低支气管肺发育不良（BPD）的发生率，但确切的机制仍不清楚。在包括 BPD 婴儿气管抽吸物在内的慢性肺部疾病中，均观察到腺苷水平升高的证据。利用一种经过充分特征描述的新生鼠肺泡发育不全模型，我们假设高氧诱导的肺泡炎症和发育不全与腺苷信号通路的改变有关。
新生鼠幼仔暴露于 14 天的高氧环境和每日咖啡因治疗，随后在室内空气中恢复 14 天。在这两个时间点收集肺部进行支气管肺泡灌洗（BAL）分析以及组织病理学和 mRNA 和蛋白质表达分析。
咖啡因治疗增加了高氧暴露新生小鼠的炎症反应并加重了肺泡发育不全。这些变化与肺泡 II 型（ATII）细胞数量减少、细胞凋亡增加和 A2A 受体表达降低有关。停止咖啡因和高氧暴露后，肺组织学恢复到与单独高氧暴露相当的基线水平。
这项研究的结果表明，咖啡因在高氧诱导的肺泡发育不全的小鼠模型中对肺泡发育可能具有潜在的不良作用。
