Effect of retinoic acid on lung injury in hyperoxia-exposed newborn rats

Abstract

To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn Sprague-Dawley rats aged 2 days were randomly assigned to 8 groups: (1) air, (2) O₂, (3) air+NS, (4) O₂+NS, (5) air+dex, (6) O₂+dex, (7) air+RA and (8) O₂+RA. Group 2, 4 6 and 8 were kept in chambers containing 85% oxygen, the values were checked 3 times a day. The other 4 groups were exposed to room air. Level of alveolarization and lung collagen were analyzed at age of 14 or 21 days through radial alveolar counts, alveolar airspace measurements, type I, II collagen immunohistochemical methods (SP method) and image processing system. Transforming growth factor-β receptors and procollagen mRNA accumulation were examined at age of 14 days through immunohistochemical methods andin situ hybridization. Our results showed that radial alveolar counts were increased and distal airspace was enlarged in group 8. Type I collagen was markedly increased, and transforming growth factor-β receptors and procollagen mRNA were decreased by retinoic acid in bronchial epithelial cells, alveolar epithelial cells and alveolar intersitium. It is concluded that retinoic acid can partially reverse lung development arrest during exposure to hyperoxia by increasing lung collagen.

Keywords

retinoic acid / hyperoxia / lung development / collagen / transforming growth factor-β receptors

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