Effects of glucocorticoid on RAGE-NF-κB pathway in hyperoxia-induced lung tissues of neonatal rats

Abstract:

Objective To explore the change of RAGE-NF-κB signaling pathway during the course of hyperoxiainduced lung injury in newborn rats, and the effect of glucocorticoid on this pathway. Methods Twenty-four Sprague- Dawley neonatal rats were randomly divided into three groups (n=8 each): sham control (control group), hyperoxiainduced acute lung injury (model group) and glucocorticoid-treated acute lung injury (glucocorticoid group). Rats were sacrificed at 13 days after birth. RAGE and NF-κB expression levels in lung tissues were detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factor α (TNF-α) and sRAGE in bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. Lung damage was evaluated by histological examinations. Results RAGE and NF-κB mRNA and protein expression levels in lung tissues were significantly increased in the model and glucocorticoid groups compared with the control group (P<0.05). Serum RAGE concentrations were significantly increased but RAGE concentrations in BALF were significantly reduced in the model and glucocorticoid groups compared with the control group (P<0.05). RAGE and NF-κB expression at both mRNA and protein levels in lung tissues was significantly lower in the glucocorticoid group than in the model group (P<0.05). RAGE concentrations were significantly lower in serum (P<0.05), but were higher in BALF (P<0.05) in the glucocorticoid group than in the model group. Conclusions RAGE-NF-κB pathway plays an important role in hyperoxia-induced lung injury in neonatal rats, and glucocorticoid administration may play a protective role against the lung injury by down-regulating RAGE-NF-κB signaling pathway.