Expression of Occludin in lung tissues of newborn rats with bronchopulmonary dysplasia and its influence on pulmonary epithelial permeability

Abstract

Objective To explore the dynamic changes of Occludin gene and protein levels in lung tissues of newborn rats with hyperoxia-induced bronchopulmonary dysplasia (BPD) in the early phase and its effect on pulmonary epithelial permeability. Methods One hundred and sixty newborn Wistar rats were randomly assigned to hyperoxia group (900 mL/L oxygen)and normoxia group (210 mL/L oxygen) according to different oxygen concentrations, 80 rats in each group.Rats were sacrificed and lung tissues were removed on 1, 3, 5, 7 d after treatment.Bronchoalveolar lavage fluid(BALF): serum FD4 ratio was detected; location and expression of Occludin were examined by immunofluorescence staining and Western blot; messenger RNA(mRNA) was studied by reverse transcription-PCR. Results There was no obvious difference in the BALF and serum FD4 ratio (1.533±0.122 vs 1.575±0.140, P>0.05) between the hyperoxia group and the normoxia group on the first day.After 3 days of hyperoxia exposure, the ratio of FD4 between BALF and serum was significantly higher than that in the normoxia group(1.365±0.159 vs 1.615±0.196, P 0.05). Compared to the normoxia group, the decrease in Occludin mRNA level was statistically significant after 3 or 5 days of hyperoxia exposure(2.46±0.27 vs 2.00±0.19, 2.62±0.28 vs 2.15±0.20, all P 0.05). Compared to the normoxia groups, the decrease in Occludin protein level was statistically significant after 5 days of hyperoxia exposure(1.03±0.04 vs 0.93±0.05, P<0.05), and after 7 days of hyperoxia exposure, the Occludin protein level dramatically declined(0.96±0.14 vs 0.65±0.07, P<0.01). There was a significantly negative correlation between Occludin protein expression and pulmonary epithelial permeability after hyperoxia exposure (r=-0.755, P<0.01). Conclusions Downregulation of Occludin hyperoxia-induced may lead to the increase of pulmonary epithelial paracellular permeability, which participates in the development of pulmonary edema in the early phase of BPD induced by hyperoxia. Key words: Occludin; Pulmonary epithelial permeability; Bronchopulmonary dysplasia; Hyperoxia; Newborn rat