Abstract：OBJECTIVE: Hyperoxia-induced lung injury is the most common cause of bronchopulmonary dysplasia (BPD) in neonates. Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that can regulate proliferation, differentiation and angiogensis of endothelial cells in neonatal lungs. This paper aimed to study the changes of VEGF expression in the lungs of neonatal rats exposed to prolonged hyperoxia so as to explore the mechanism of BPD. METHODS: Wistar rat pups were randomized to hyperoxia (Hyperoxia group, FiO_2=0.95) or room air exposure (Normoxia group) (both n=30) from postnatal 12 hrs. The rats were sacrificed at postnatal days 1, 2, 3, 7, 14 and 21 (5 rats each time point) and their lungs were collected. The lung sections were stained with hematoxylin and eosin for histological evaluation. Expressions of VEGF protein and mRNA were detected by immunohistochemistry and in situ hybridization. Results were expressed as gray values. The higher the value, the lower the expressions. RESULTS: After being exposed to hyperoxia for 7 days, lung tissues developed interstitial fibrosis, abnormal vascular constitution and a decreased alveolar septation. These changes became more obvious with the time of prolonged hyperoxia exposure. Expressions of VEGF protein at 3 and 7 days of exposure in the Hyperoxia group decreased significantly as compared with the Normoxia group (81.9±0.8 vs 80.8±1.0,82.8±1.2 vs 79.2±1.6,P<0.01). The expression of VEGF mRNA in the Hyperoxia group was also lower at 3 and 7 days of exposure (89.5± 1.1 vs 88.0±1.0, 91.1±1.5 vs 87.7±1.7, P<0.001). Both VEGF protein and mRNA levels gradually decreased with the hyperoxia exposure time and their levels could not be detected at 14 and 21 days of hyperoxia exposure. CONCLUSIONS: Hyperoxia exposure inhibited the expression of lung VEGF in neonatal rats, which may be the underlying mechanism of hyperoxia-induced BPD.
LIU Bo,LIU Xue-Yan,LI Juan et al. Exposure to prolonged hyperoxia decreases the expression of vascular endothelial growth factor in lungs of neonatal rats[J]. CJCP, 2005, 7(5): 447-450.
