宫内缺氧对新生大鼠肺血管发育及肺血管内皮生长因子表达的影响

Influence of intrauterine hypoxia on the lung blood vessel development in rats after birth and expression of VEGF in the lung

目的:观察宫内缺氧对新生大鼠常压、常氧生存状态下肺发育的影响,及对新生大鼠不同生存时间肺组织血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达变化,为探讨宫内缺氧患儿出生后的治疗方案提供实验依据。方法:建立宫内缺氧模型。实验分为空气对照组(对照组)和缺氧6 d组(缺氧组)。两组大鼠出生后均置于常压、常氧下饲养。分别于出生时、出生后第7天、第14天及第21天行肺血管形态检测,以免疫组织化学方法测定肺组织VEGF蛋白表达,实时(real time)-PCR测定肺组织VEGF mRNA表达及电子显微镜下观察肺血管内皮细胞变化。结果:随着日龄增长,缺氧组与对照组肺组织VEGF蛋白及mRNA表达均逐渐增加,缺氧组增长幅度减慢,增长曲线与对照组呈交叉现象。缺氧组与对照组大鼠出生后各时间点肺血管形态无明显差异。随着日龄增长,缺氧组内皮细胞增生较出生时减少;内皮细胞水肿明显,于第14天达高峰。结论:宫内缺氧新生大鼠肺VEGF表达增长幅度减慢,VEGF表达影响大鼠生后肺血管发育。

Objective：To observe the effect of intrauterine hypoxia on the development of rat lung atfer birth under ordinary presure and normoxia, on the expression of vascular endothelial growth factor （VEGF） in the lung as the age increasing after birth, and to provide experimental basis for the treatment of intrauterine hypoxia atfer baby was born.Methods：Intrauterine hypoxia models were established. The rats were divided into an air-control group （the control group） and a hypoxic 6-day group （the hypoxic group）. All rats were fed under normal pressure and normoxia atfer they were born. At postnatal 7, 14, and 21 days, we measured the pulmonary vascular morphometry, detected the expression of VEGF protein with immunohistochemisty, the expression of VEGF mRNA with real-time PCR, and observed the alteration of capillary endothelium in the lung tissues under the electron microscope. Results：hTe expression of VEGF protein and VEGF mRNA in the 2 groups increased as the rats grew, but the expression increased slower in the hypoxic group than that in the control group. hTe increase curve of the 2 groups crossed. hTere was no signiifcant difference between the 2 groups in the pulmonary vascular morphometry at each experiment time point. Hyperplasia of capillary endothelium decreased with age. Cellular edema of capillary endothelium was obvious especially at the 14th day atfer birth under the electron microscope. Conclusion：hTe expression of VEGF protein and VEGF mRNA has slower increase in the intra-uterine hypoxic rats than that in the normal control rats. hTe expression of VEGF may inlfuence the development of lung vessel atfer rats was born.