高浓度氧对新生大鼠肺血管内皮生长因子及其受体表达的影响

Effects of prolonged exposure of high concentration of oxygen on expression of vascular endothelial growth factor and its receptors in neonatal rat lungs

摘要:

目的:研究持续吸入75%氧对新生大鼠肺血管内皮生长因子（vascular endothelial growth factor，VEGF）及其受体（VEGFR1和VEGFR2）表达的影响，探讨较高浓度吸氧对肺血管发育的影响及与支气管肺发育不良（bronchopulmonary dysplasia，BPD）的关系。方法:新生足月Sprague-Dawley大鼠48只，随机分为对照组和实验组。实验组生后12 h开始持续吸入75%氧气。分别于实验开始后的7 d、14 d和21 d处死留取肺组织标本，苏木精-伊红染色观察病理改变，免疫组化检测VEGF及其受体蛋白表达，RT-PCR检测其mRNA表达。结果实验组大鼠肺组织结构发生类似“新型”BPD的病理改变。75％氧暴露21 d时，VEGF（10.9±2.7 vs 30.8±6.4）、VEGFR1（5.4±1.4 vs 15.6±3.4）和VEGFR2（11.3±2.6 vs 21.7±4.5）的蛋白表达均较对照组减少（P<0.05）；VEGF（1.6 vs 3.3）、VEGFR1（0.4 vs 6.6）及VEGFR2（0.5 vs 4.9）的mRNA表达均较对照组减少（P<0.05）。结论:在新生大鼠中，长时间吸入较高浓度氧可能通过抑制肺血管发育导致BPD的发生。［中国当代儿科杂志，2009，11（11）：927-930］

Abstract:

OBJECTIVE: To study the effects of prolonged 75% oxygen exposure on the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) in the neonatal rat lungs and to elucidate the effects of prolonged exposure of high concentration of oxygen on lung vascular development and its relationship with bronchopulmonary dysplasia (BPD). METNODS: Forty-eight Sprague-Dawley rat pups were randomly exposed to air (control group) and 75% oxygen (experimental group) 12 hrs after birth. The rats were sacrificed 7, 14 and 21 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation. Expression of VEGF, VEGFR1 and VEGFR2 protein and mRNA was detected by immunohistochemistry and RT-PCR. RETHODS: After being exposed to 75% oxygen for 21 days, lung tissues had pathological changes as “new” BPD. Expressions of VEGF protein (10.9±2.7 vs 30.8±6.4), VEGFR1 protein (5.4±1.4 vs 15.6±3.4) and VEGFR2 protein (11.3±2.6 vs 21.7±4.5) on day 21 in the experimental group decreased significantly as compared with the control group (P<0.05). The expression of VEGF mRNA (1.6 vs 3.3), VEGFR1 mRNA (0.4 vs 6.6) and VEGFR2 mRNA (0.5 vs 4.9) on day 21 in the experimental group also decreased significantly as compared with the control group (P<0.05). CONCLUSIONS: Prolonged exposure of high concentration of oxygen may cause BPD possibly by inhibiting lung vascular development in neonatal rats.［Chin J Contemp Pediatr, 2009, 11 (11):927-930］