Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation

Abstract

Background: One out of four children with neonatal asphyxia has lung involvement. Still, there has been little research on injury mechanisms of hypoxia-reoxygenation in the neonatal lung. Objectives: To make a temporal profile of the gene expression changes of 44 a priori selected genes after hypoxia-reoxygenation in the newborn mouse lung, and to compare the changes after hyperoxic and normoxic reoxygenation. Methods: Postnatal day 7 mice were randomized to 2-hour hypoxia (8% O₂) and 30-min reoxygenation in either 60% O₂ or air. After 0-72 h of observation, gene expression changes and protein concentrations in whole lung homogenates were examined. Results: Immediately after completed reoxygenation, 7 genes of mediators of inflammation were downregulated, and there was an antiapoptotic gene expression pattern. Three DNA glycosylases were downregulated, while genes involved in cell cycle renewal indicated both increased and decreased cell cycle arrest. Sod1 (T2.5h median H60: 1.01, H21: 0.88, p = 0.005; T5h median H60: 1.04, H21: 0.85, p = 0.038) and Il1b (T0h median H60: 0.86, H21: 1.08, p = 0.021) were significantly differentially expressed when comparing hyperoxic and normoxic reoxygenation. Conclusion: In this newborn mouse lung hypoxia-reoxygenation model, we found downregulation of genes of mediators of inflammation, an antiapoptotic gene expression pattern, and downregulation of DNA glycosylases. Sod1 and Il1b were significantly differentially expressed when comparing reoxygenation using 60% O₂ with air.