高氧对胎儿肺气道及血管发育的影响及地塞米松的干预作用

Effect of hyperoxia on the airway and vascular development in fetal lung and the intervention of dexamethasone

目的探讨高氧对人胎儿肺泡及肺血管发育的影响及地塞米松的干预作用。方法假腺体期胎儿肺组织分别于高氧（95％O2，5％CO2）及正常氧（21％O2，5％CO2）中培养72h，两组又分别同时加入地塞米松（10^-6mol／L），对照组以相同浓度乙醇代替。收获的肺组织分别以细胞角蛋白和CD31确定上皮细胞及内皮细胞，用图像分析系统计算出气道厚度、气道占组织百分比、血管距最近气道距离、血管占间质比例。结果空气培养72h，肺结构与新鲜肺组织比较无明显变化；高氧组气道明显扩张，上皮明显变薄，气道所占比例明显增加（P〈0．05）。高氧组肺间质毛细血管明显靠近气道（50μm），该组血管所占面积（4．0％）明显小于正常氧（4.2％）和高氧＋地塞米松组（5．4％）（P〈0．05）。地塞米松可抑制高氧对肺组织的不良效应。结论高氧导致胎儿肺组织气道简单化及间质血管减少；地塞米松可阻止这些变化，促进肺成熟。

Objective To investigate the effects of dexamethasone on the airway development and vasculogenesis in cultured human fetal lung exposed to hyperoxia. Methods Human fetal lung at the pseudoglandular stage of development were cultured either in norrnoxia（21% O2, 5% CO2） or hyperoxia （95% O2, 5% CO2） for 72 hours. Dexamethasone was added into the culture medium at the concentration of 10^-6 mol/L, whereas ethanol at the same concentration was as control. Harvested tissue was stained for pancytokeratin to identify epithelial cells, CD31 as a specific antibody of endothelial cell. The effects of lung morphometry were analyzed using computer-assisted image analysis software to calculate the thickness of airways, surface area occupied by airways and the distance of vessels to the nearest airway as well as the surface area of blood vessels. Results The lung architecture remained largely unchanged in normoxia for 72 hours culture, whereas hyperoxic culture of lungs resulted in significant dilation of airways and thinning of epithelium, The surface area occupied by airways increased significantly （ P 〈 0.05 ）. The blood vessels in interstium were more close to the airway epithelium in the hyperoxic lung （50μm） as compared with normoxia group. Meanwhile, the proportion of the blood vessels in interstium of hyperoxia group （4.0%） was higher than those of normoxia group （4.2 % ） and hyperoxia with dexamethasone （5.4 % ）（ P 〈 0.05 ）. Dexamethasone has the protective effect on lungs exposed to hyperoxia. Conclusion Our results showed that hyperoxia resulted in the simple airways and the decreased blood vessel density in interstitium of cultured human fetal lung. Dexamethasone has protective effect on fetal lungs exposed to hyperoxia and can promote lung mature.