Influence of intrauterine hypoxia on lung blood vessel development in rats and expression of vascular endothelial growth factor in the lungs / 中华围产医学杂志

ABSTRACT

Objective To observe the impact of intrauterine hypoxia on the development of rat lungs and expression of vascular endothelial growth factor (VEGF) in the lungs as the time of hypoxia was extended.Methods To create a model of intrauterine hypoxia,12 pregnant rats were divided into four groups as followsair-control group,hypoxic 2-day group,hypoxic 6-day group,and hypoxic 10-day group.At birth,we performed pulmonary vascular morphometry in newborn rats with Nis software,and measured pulmonary arterial diameter,wall thickness and wall thickness/pulmonary arterial diameter.We detected expression of VEGF protein by immunohistochemistry and mRNA by real-time polymerase chain reaction.Changes in pulmonary capillary endothelium under electron microscope were observed.One-way analysis of variance and the Student Newman Keuls q (SNK-q) test were applied for statistical analysis.Results As the hypoxic time was extended,wall thickness and wall thickness/pulmonary arterial diameter increased.Compared with the air-control group,pulmonary vascular wall thickness in the hypoxic 10-day group increased [(16.4 ± 5.9) vs (10.8±2.8) μm; q=-8.04,P＜0.05].Wall thickncss/pulmonary artcrial diameter in the hypoxic 10-day group increased compared with that in the air control group,hypoxic 2-day group and hypoxic 6-day group [(31.3±5.1) ％,(22.2±4.9) ％and (23.6±3.9) ％vs (24.1±3.9) ％;q=-7.08,-4.92 and-5.0,all P＜0.05].Expression of VEGF protein in the lungs increased in the hypoxic 6-day group compared with the air-control group [(13.7±3.9) ％ vs (9.3±3.5) ％; q=-6.83,P＜0.05],while the expression was higher in hypoxic 10-day group than in the air-control group and hypoxic 2-day group [(15.2±4.7) ％,(9.3±3.5) ％ vs (11.8 ± 3.3) ％] (q=-9.16 and-5.19,all P＜0.05).Expression of VEGF mRNA in the lungs increased in the hypoxic 6-day group compared with the air-control group [(1.6±0.2)vs (0.8 ±0.2); q=-5.07,P＜0.05],while the expression was higher in the hypoxic 10 day group than in the air-control group and hypoxic 2-day group [(2.2±0.3),(0.8±0.2) vs (1.3±0.2)] (q=-9.54 and-6.42,all P＜0.05).Electron microscopy showed puhnonary capillary endothelial cell swelling as the hypoxic time was extended.In the air-control group,there was no capillary endothelial cell hyperplasia and swelling; in hypoxic 2-day group,there was mild swelling of the capillary endothelial cells and a small amount of hyperplasia; in hypoxic 6-day group,there was moderate swelling of the capillary endothelial cells; and in hypoxic 10-day groupthere was significant swelling of the capillary endothelial cells,and pyknosis.Conclusions Intrauterine hypoxia resulted in higher expression of VEGF protcin and mRNA.VEGF in the lungs of newborn rats was involved in the vascular development process.