血管内皮生长因子在肺出血新生鼠肺组织中的表达及其作用

Expression and Role of Vascular Endothelial Growth Factor in Pulmonary Tissue of Newborn Rats with Pulmonary Hemorrhage

目的探讨血管内皮生长因子（VEGF）在肺出血新生鼠肺组织中的表达及其作用。方法生后7～8dWistar新生鼠，随机分为正常对照组（C组）、缺氧组（H组）、低温缺氧组（HH组）、低温缺氧后常氧复温组（HHR组）及低温缺氧后高氧复温组（HHRO2组）。C组置常温室内；H组置缺氧箱内6h，吸氧体积分数为50～60mL／L；HH组置（10±1）℃冰箱内6h，吸氧体积分数同上；HHR组结束上述低温缺氧6h后予常氧下复温2h；HHRO2组同HHR组，但吸氧体积分数〉95mL／L。取各组大鼠肺组织，观察肺大体情况，切片HE染色观察肺组织病理学改变，逆转录-聚合酶链反应（RT-PCR）方法检测其肺组织VEGFmRNA表达。结果H、HH、HHR和HHRO2组肺大体均呈现水肿，HH、HHR和HHRO2组可见点状、局灶至弥散性肺出血；各实验组组织学改变包括肺泡及间质水肿、间隔断裂、肺泡扩张及融合、肺泡出血，以HHRO2组最严重；VEGF188 mRNA在H、HH组表达明显增高，与C组比较有显著差异（P〈0．05，0．01）；HHR和HHRO2组表达亦增高，但与C组比较差异无显著性。绪论低温缺氧后复温供氧所致肺出血新生鼠肺组织水肿，可能与有明显血管通透作用的VEGF表达增高有关。

Objective To investigate the expression and role of vascular endothelial growth factor （VEGF） in pulmonary tissue of newborn Wistar rats with pulmonary hemorrhage. Methods Newborn Wistar rats were randomly divided into control group （ group C） and four experimental groups [ group H （ hypoxia）, HH （ hypoxia/hypethermia）, HHR （ hypoxia/hypothermia and rewarming with air）, HHRO2 （hypoxia/hypothermia and rewarming with hyperoxia）]. Group C were exposed to normothermia inhaling room air, group H to hypoxia （50 - 60 mL/L O2 ） for 6 hours, group HH to hypothermia （ 10±1 ） ℃ and hypoxia （50 - 60 mL/L O2 ） for 6 hours, group HHR to hypothermia （ 10 ± 1 ） ℃ and hypoxia for 6 hours and then to hyperthermia（ 37 ℃ ） inhaling room air for 2 hours, group HHRO2 to hypothermia （ 10 ± 1 ） ℃ and hypoxia for 6 hours and then to hyperthermia （ 37 ℃ ） and reoxygen （ 〉 95 mL/L O2 ） for 2 hours. The gross anatomical and histological changes （HE staining）in lungs were observed, VEGF mRNA expressions were studied by reverse transcription polymerase chain reaction （RT- PCR）. Results Lungs of experimental groups represented edema, inaddition, punctiform, local and diffuse pulmonary hemorrhage were observed in groups of HH, HHR and HHRO2. Histopathological changes included pulmonary alveoli and interstitial edema, spacer breaking, pulmonary alveolidilating, fusion and hemorrhage,in which the most severe cases involved in group HHRO2. VEGF 188 mRNA expression increased significantly in group H and HH （P 〈 0. 05,0. 01, respectively）and also increased in group HHR and HHRO2 ,but no significant differences could be observed compared with group C, Conclusion Overexpression of VEGF, which can cause vascular hyperperme- ability, may contribute to pulmonary edema occurring in the process developing pulmonary hemorrhage in newborn rats subjected hypothennia - hypoxia/rewarming - reoxygenating.