Division of Neonatology, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
BMC Pulm Med. 2024 Nov 25;24(1):584. doi: 10.1186/s12890-024-03391-1.
Prolonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice.
C57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O) conditions for 6 days. Control, low (5 ng/neonate) and high (25 ng/neonate) doses of VitD were administered daily beginning at day 2 via oral gavage. Lung tissue was analyzed for edema, changes in pulmonary structure and function, and inflammatory cytokine expression.
Neonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant changes in cytokine expression were observed between untreated and VitD neonates. While changes in surfactant protein mRNA expression were impacted by hyperoxia and VitD administration, no significant changes in alveolar type II cell percentages were observed. At 3 weeks, mice in hyperoxia treated with VitD had greater lung compliance, diminished airway reactivity and improved weight gain.
High dose VitD significantly limited harmful effects of HALI. These results suggest that supplementation of VitD to neonatal mice during hyperoxia exposure provides both short-term and long-term protective benefits against HALI.
早产儿长时间暴露在高氧环境中会导致高氧急性肺损伤（HALI）。维生素 D（VitD）可刺激肺成熟并发挥抗炎作用。我们的目的是确定 VitD 是否通过降低炎症细胞因子表达和改善肺泡化和肺功能来提供对 HALI 的剂量依赖性保护作用。
C57BL/6 新生小鼠随机分为空气组或高氧（85% O）组，分别于生后第 2 天起每日通过口服灌胃给予 VitD（对照组、低剂量[5ng/新生鼠]和高剂量[25ng/新生鼠]）。分析肺组织水肿、肺结构和功能变化以及炎症细胞因子表达。
与高氧未治疗组相比，高氧条件下 VitD 治疗的新生鼠体重增加改善，肺水肿减轻，肺泡表面积增加。与未治疗的 VitD 新生鼠相比，细胞因子表达无明显变化。尽管表面活性蛋白 mRNA 表达受高氧和 VitD 给药的影响，但肺泡 II 型细胞比例无明显变化。在 3 周时，高氧暴露中 VitD 治疗的小鼠肺顺应性增加，气道反应性降低，体重增加。
高剂量 VitD 显著限制了 HALI 的有害影响。这些结果表明，在高氧暴露期间对新生鼠补充 VitD 可提供短期和长期的 HALI 保护作用。
