[Relation of insulin-like growth factor binding protein-2 with hyperoxia-induced lung injury in term and premature neonatal rats]

Abstract

Objective: To study the deleterious effect of prolonged hyperoxic exposure on term and premature neonatal rat lungs and investigate the relationship between insulin-like growth factor binding protein (IGFBP)-2 and hyperoxia-induced lung injury in neonatal rats.

Methods: At the 22nd postnatal day Sprague-Dawley (SD) term-newborn or preterm-newborn rats were randomly divided into 4 groups. group I: term-rats+air group; group II: term-rats+hyperoxia group; group III: preterm-rats+air group; group IV: preterm-rats+hyperoxia group. The rats in group II and IV were exposed to about 85% (in volume) O(2). The rats in group I and III were exposed to air in the same rooms. At 4, 7, 10, 14 and 21 days after birth, eight rats in each group were killed. The mortality of newborn rats was also recorded and lung radical alveolar counts (RAC) were examined. Lung histopathology with hematoxylin and eosin (HE) staining was examined; The protein and mRNA of IGFBP-2 in the lung tissue were determined by Western blotting and by reverse transcription-polymerase chain reaction (RT-PCR).

Results: After 7 days of 85% O(2) exposure, the survival rate in group II, IV were significant lower compared with group I, III (all P<0.01), but no difference was found between group IV and group II (P>0.05). No inflammatory change in lung tissue was found in group I and III. After 7-14 days of hyperoxia exposure, blood vessels in group II, IV were dilated. Red blood cells and inflammatory cells were seen infiltrating into the alveolar space, and interstitium was thickened. After 21 days of hyperoxic exposure, inflammatory changes in group II became more marked, and the alveolar walls or alveolar septa were markedly thickened. The formation of alveoli in group II, IV was retarded and RACs at all time points were significantly lower than those in group I, III (all P<0.01). After 4 days and 14 days, the expression of IGFBP-2 in the group II and IV were significantly higher than those in group I, III (all P<0.01). The expression of mRNA of IGFBP-2 showed the same tendency of the protein in all 4 groups.

Conclusion: The prolonged exposure to hyperoxia may cause subacute lung injury and the retardation of lung development in term-neonatal or preterm-neonatal rats. The abnormal expressions of IGFBP-2 correlate with hyperoxia-induced lung injury in neonatal rats.