Liang Fei, Zhu Jian-xing, Xia Hong-ping, Li Hui-ping, Zhu Lü-chang
Department of Pediatrics, Shanghai Jiao Tong University, Shanghai, China.
Zhonghua Er Ke Za Zhi. 2011 Nov;49(11):834-8.
To study the effects of prolonged 85% oxygen exposure on lung vascular development and the expression of angiopoietin-1 (Ang-1) in the neonatal rat lungs.
Ninety-six Sprague-Dawley rat pups were randomly exposed to air (control group) and 85% oxygen (experimental group) 6 hrs after birth. The rats were sacrificed 3, 7 and 14 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation and analysis of vessel volume density. Expressions of angiopoietin-1 (Ang-1) in lung tissue were measured by immunohistochemistry. Expression of Ang-1 protein and mRNA was detected by Western Blot and Real time-PCR.
After being exposed to 85% oxygen for 14 days, lung tissues had pathological changes as "new" bronchopulmonary dysplasia (BPD). The RAC on day 7 and day 14 in experimental group decreased significantly as compared with the control group [(10.55 ± 0.13) vs. (11.74 ± 0.19), (12.47 ± 0.05) vs. (15.03 ± 0.16), P < 0.05]. The X-ray showed that the diameter of lung vessel was much smaller and the vessels had less branches in experimental group compared with the control group on day 14. The vessel volume density on day 14 in experimental group decreased significantly as compared with the control group [(3.55 ± 0.09) vs. (6.03 ± 0.16), P < 0.05]. Immunohistochemistry and Western blotting showed that the expressions of Ang-1 protein on day 7 and day 14 in the experimental group decreased significantly as compared with the control group [(4.27 ± 0.34) vs. (3.10 ± 0.29), P < 0.05, (5.65 ± 0.49) vs. (3.21 ± 0.28), P < 0.01], [(0.88 ± 0.31) vs. (0.41 ± 0.12), P < 0.05, (0.90 ± 0.29) vs. (0.21 ± 0.06), P < 0.01]. The expressions of Ang-1 mRNA on day 7 and day 14 in the experimental group also decreased significantly as compared with the control group [(0.85 ± 0.14) vs. (0.44 ± 0.21), P < 0.05, (0.87 ± 0.24) vs. (0.24 ± 0.05), P < 0.01].
Prolonged exposure of high concentration of oxygen may cause impairment of lung vascular development by inhibiting expression of Ang-1 in neonatal rats, which is likely to contribute to pathogenesis of BPD.
研究长时间暴露于85%氧气对新生大鼠肺血管发育及血管生成素-1（Ang-1）在新生大鼠肺组织中表达的影响。
96只Sprague-Dawley新生大鼠幼崽出生后6小时随机分为空气暴露组（对照组）和85%氧气暴露组（实验组）。暴露后3天、7天和14天处死大鼠并取肺组织样本。肺组织切片进行苏木精-伊红染色用于组织学评估及血管容积密度分析。采用免疫组织化学法检测肺组织中血管生成素-1（Ang-1）的表达。通过蛋白质印迹法和实时荧光定量PCR检测Ang-1蛋白及mRNA的表达。
暴露于85%氧气14天后，肺组织出现“新型”支气管肺发育不良（BPD）的病理改变。实验组第7天和第14天的RAC较对照组显著降低[（10.55±0.13）对（11.74±0.19），（12.47±0.05）对（15.03±0.16），P<0.05]。X线显示，第14天实验组肺血管直径较对照组小得多且分支较少。实验组第14天的血管容积密度较对照组显著降低[（3.55±0.09）对（6.03±0.16），P<0.05]。免疫组织化学和蛋白质印迹法显示，实验组第7天和第14天的Ang-1蛋白表达较对照组显著降低[（4.27±0.34）对（3.10±0.29），P<0.05，（5.65±0.49）对（3.21±0.28），P<0.01]，[（0.88±0.31）对（0.41±0.12），P<0.05，（0.90±0.29）对（0.21±0.06），P<0.01]。实验组第7天和第14天的Ang-1 mRNA表达较对照组也显著降低[（0.85±0.14）对（0.44±0.21），P<0.05，（0.87±0.24）对（0.24±0.05），P<0.01]。
长时间暴露于高浓度氧气可能通过抑制新生大鼠Ang-1的表达导致肺血管发育受损，这可能是BPD发病机制的原因之一。
