Prevention of bronchopulmonary dysplasia (BPD) in premature-birth babies continues to be an unmet medical need. Intramuscular Vitamin A is currently employed in preterm neonates to prevent BPD but requires intramuscular (IM) injections in fragile neonates. We hypothesized that non-invasive inhaled delivery of vitamin A, targeted to lung, would be a more effective and tolerable strategy. We employed our well-established hyperoxia-injury neonatal rat model, exposing newborn rats to 7 days of constant extreme (95% O₂) hyperoxia, comparing vitamin A dosed every 48 hours via either aerosol inhalation or IM injection, with normoxic untreated healthy animals and vehicle-inhalation hyperoxia groups as positive and negative controls, respectively. Separately, similar vitamin A dosing of normoxia-dwelling animals was performed. Analyses after day 7 included characterization of alveolar histomorphology, and protein biomarkers of alveolar maturation [surfactant protein C (SP-C), peroxisome proliferator-activated receptor (PPAR) g, cholinephosphate cytidylyl transferase, vascular endothelial growth factor and its receptor, FLK-1, and retinoid X receptors (RXR-α, -β, and -γ], apoptosis [Bcl2 and Bax] key injury repair pathway data including protein markers [ALK-5 and β-catenin] and neutrophil infiltration, and serum vitamin A levels. Compared with IM dosing, inhaled vitamin A significantly enhanced biomarkers of alveolar maturation, mitigated hyperoxia-induced lung damage, and enhanced surfactant protein levels, suggesting that it may be more efficacious in preventing BPD in extremely premature infants than the traditionally used IM dosing regimen. We speculate lung-targeted inhaled vitamin A may also be an effective therapy against other lung damaging conditions leading to BPD or, more generally, to acute lung injury.

中文翻译：

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在支气管肺发育不良的新生大鼠模型中，吸入维生素 A 在减轻高氧引起的肺损伤方面比肌肉注射更有效。

预防早产儿支气管肺发育不良 (BPD) 仍然是一项未得到满足的医疗需求。肌肉注射维生素 A 目前用于早产儿预防 BPD，但需要对脆弱的新生儿进行肌内 (IM) 注射。我们假设针对肺部的非侵入性吸入维生素 A 将是一种更有效和可耐受的策略。我们采用了我们完善的高氧损伤新生大鼠模型，将新生大鼠暴露在持续极端的 7 天（95% O ₂) 高氧，比较通过气溶胶吸入或肌肉注射每 48 小时给药一次的维生素 A，与常氧未处理的健康动物和载体吸入高氧组分别作为阳性和阴性对照。另外，对常氧动物进行了类似的维生素 A 给药。第 7 天后的分析包括肺泡组织形态学特征和肺泡成熟的蛋白质生物标志物 [表面活性蛋白 C (SP-C)、过氧化物酶体增殖物激活受体 (PPAR) g、磷酸胆碱胞苷酰转移酶、血管内皮生长因子及其受体、FLK- 1、类视黄醇 X 受体（RXR-α、-β 和 -γ]、细胞凋亡 [Bcl2 和 Bax] 关键损伤修复途径数据，包括蛋白质标志物 [ALK-5 和 β-连环蛋白] 和中性粒细胞浸润，以及血清维生素 A水平。与 IM 给药相比，吸入维生素 A 显着增强了肺泡成熟的生物标志物，减轻了高氧引起的肺损伤，并提高了表面活性蛋白水平，这表明它在预防极早产儿 BPD 方面可能比传统使用的 IM 给药方案更有效。我们推测肺部靶向吸入维生素 A 也可能是一种有效的治疗方法，可以对抗导致 BPD 或更普遍地导致急性肺损伤的其他肺损伤疾病。