重组人促红细胞生成素对慢性高氧致支气管肺发育不良的保护作用

Effect of recombinant human erythropoietin on chronical hyperoxia-induced bronchopulmonary dysplasia

探讨重组人促红细胞生成素(recombinant human erythmpoietin,rhEPO)作为血管生长样因子对高氧致新生大鼠支气管肺发育不良(bronchopulmonary dysplasia,BPD)的血管保护作用。将96只新生Wistar大鼠生后1h随机分为4组:(1)空气对照,(2)空气+rhEPO,(3)高氧对照,(4)高氧+rhEPO。第3、第4组置于玻璃氧箱中,持续输入氧气,FIO2=850ml/L,第2、第4组于生后即刻、高氧暴露前30min和生后2d给rhEPO 2400IU/kg背部皮下注射,第1、第3组给予等量生理盐水注射。于生后第3、7及10d采集肺组织标本,光镜下观察肺组织学改变,应用免疫组化测定肺组织织血管内皮标志CD31及肺血管内皮细胞生长因子(vascular endothelial growth factor VEGF)表达的变化。研究发现:与高氧组相比,高氧+rhEPO组大鼠肺组织CD31阳性面积比和VEGF的表达明显增高;3d增高,10d达高峰。结果提示:rhEPO(2400IU/kg)可以促进肺血管的发育和修复,对高氧致新生鼠BPD有血管保护作用。

To investigate effect of recombinant human erythropoietin（rhEPO） as angiogenesis--like factor,on chronic lung disease exposed to hyperoxia in newborn rats. Ninty six Wistar newborn rats were randomly divided into four groups with lh after birth：room ai-exposed control group, room air-exposed rbEPO treated group, hyperoxia-exposed group, hyperoxia-exposed rhEPO treated group. The last two groups were exposed to oxygen, FiO2 = 850mL/L, room air-exposed rhEPO treated and hyperoxia exposed rhEPO treated group received rhEPO 2400 IU/kg subcutaneously at birth,before thirty minutes exposed to oxygen and 2 days after birth. The isodose of 9g/Lsaline were given in the same way in room air-exposed controls and hyperoxi a-exposed pups. Rats from per group were sacrificed on 3,7and 10d. Lung histology was observed under microscope, CD31 and vascular endothelial growth factor（VEGF） expression were measured by immunohistochemistry. Results in hyperoxia＋ rhEPO group, expression of lung CD31 and VEGF in newborn rats were significantly higher than those in hyperoxia group, increased on 3d and reached peakl0d. Conclusion rhEPO（2400IU/kg） have protective effect and accelerate growth on pulmonary vessels in hyperoxia-induced BPD of newborn rats.