ABSTRACT Hyperoxia‐induced bronchopulmonary dysplasia (BPD) is associated with the abnormal development of lungs in preterm infants. However, its molecular pathogenesis remains unclear. This study aimed to evaluate the genetic and metabolic consequences of hyperoxic lung injury in neonatal rats with BPD and determine the underlying molecular mechanisms. Hyperoxia treatment was used to establish BPD in neonatal rats. Histopathological analysis of the lung tissues was performed using hematoxylin and eosin staining. An integrated transcriptomic and metabolomic analysis was performed to identify the associated molecular functions and pathways. Histopathological analysis revealed that hyperoxia reduced the number of alveolar cells and increased their interval and volume. Transcriptomic and metabolomic analyses identified differentially expressed genes and metabolites in the lung tissue of neonatal rats with BPD, which were related to metabolic pathways modulating antioxidant activity, particularly glutathione metabolism; alanine, aspartate, and glycine metabolism; taurine and hypotaurine metabolism; and arginine and proline metabolism. We observed a decrease in metabolites and an increase in genes involved in antioxidant metabolic pathways in neonatal rats with BPD, indicating the concurrent upregulation of oxidative stress responses. Our findings indicate that BPD progression is linked to oxidative stress and disrupted amino acid metabolism, particularly in glutathione, taurine/hypotaurine, and arginine/proline pathways. This integrated multi‐omics approach reveals potential therapeutic targets for BPD treatment.
Jia et al. (Mon,) studied this question.