Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development
Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development
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DOI：
10.1165/rcmb.2004-0287oc
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发表时间：
2005-05-01
影响因子：
6.4
通讯作者：
Tuder, RM
中科院分区：
文献类型：
--
作者：
McGrath-Morrow, SA;Cho, C;Tuder, RM
血管内皮生长因子（VEGF）是出生后肺正常发育所必需的，可能是高氧暴露后肺结构损伤的基础。为了确定血管内皮生长因子受体（VEGFR）2和1对出生后肺生长的单独作用，在围产期用抗血管内皮生长因子受体（VEGFR）-2（DC 101）或血管内皮生长因子受体（VEGFR）-1（MFI）的中和抗体治疗新生小鼠。在1周龄时，在生命的第2天和第4天用DC 101处理的小鼠具有与受损的肺泡形成一致的显著更大的平均肺泡直径。然而，到2周龄时，围产期处理的DC 101小鼠具有正常的肺泡结构。暴露于围产期高氧（O-2）的小鼠在1周龄时也有较大的平均肺泡直径，但与DC 101治疗的小鼠不同，它们的有丝分裂指数在1周龄时降低，并且它们在生命的前2周后持续肺泡扩大。O-2处理的肺在1周龄时也有caspase 3的增加，在2周龄时硝基酪氨酸的表达显著增加。因此，在围产期阻断VEGFR-2会破坏早期肺泡发育，但这种作用随着时间的推移是可逆的，而高氧肺损伤与持续的肺结构损伤相关。
Vascular endothelial growth factor (VEGF) is necessary for normal postnatal lung development and may underlie the structural lung damage that follows hyperoxic exposure. To determine the individual roles of VEGF receptors (VEGFR) 2 and 1 on postnatal lung growth, neonatal mice were treated with neutralizing antibodies to VEGFR-2 (DC101) or VEGFR-1 (MFI) in the perinatal period. At 1 wk of age, mice treated with DC101 on Days 2 and 4 of life had significantly larger mean alveolar diameters consistent with impaired alveolization. By 2 wk of age, however, perinatally treated DC 101 mice had normal-appearing alveolar structure. Mice exposed to perinatal hyperoxia (O-2) also had larger mean alveolar diameters at 1 wk of age, but unlike DC101-treated mice, their mitotic index was decreased at 1 wk of age and they had persistent alveolar enlargement beyond the first 2 wk of life. The O-2-treated lung also had an increase in caspase 3 at 1 wk of age and significantly greater expression of nitrotyrosine at 2 wk of age. Therefore, VEGFR-2 blockade in the perinatal period disrupts early alveolar development, but the effect is reversible with time, whereas hyperoxic lung injury is associated with ongoing lung structural impairment.