Janér Joakim, Andersson Sture, Haglund Caj, Karikoski Riitta, Lassus Patrik
Hospital for Children and Adolescents, Helsinki, Finland.
Pediatrics. 2008 Aug;122(2):340-6. doi: 10.1542/peds.2007-1941.
We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants.
Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of <2 days and 7 with respiratory distress syndrome of >10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week.
In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity.
The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia might be a reflection of the dysregulation of vascular development that is characteristic of bronchopulmonary dysplasia.
我们研究了新生儿肺发育、急性和慢性肺损伤过程中两种促血管生成因子，即胎盘生长因子和血管内皮生长因子受体-2在肺中的表达情况。
对胎盘生长因子和血管内皮生长因子受体-2进行免疫组织化学研究，共纳入6组，即9例胎儿、4例早产和8例足月出生后不久死亡且无肺损伤的婴儿、5例出生后<2天的呼吸窘迫综合征早产儿、7例出生后>10天的呼吸窘迫综合征早产儿以及6例支气管肺发育不良患儿。在出生后第一周内，对20例早产儿的70份气管吸出液样本进行胎盘生长因子浓度测定。
免疫组织化学分析显示，所有组的支气管上皮和巨噬细胞中均可见胎盘生长因子染色。远端气道上皮阳性主要见于胎儿和出生后不久死亡的早产儿。所有组的血管内皮中均可见血管内皮生长因子受体-2染色，胎儿的淋巴管内皮中也可见该染色。动脉内皮中的血管内皮生长因子受体-2染色与胎龄较大相关，静脉内皮中的染色与胎龄较小相关。在毛细血管中，支气管肺发育不良患儿的血管内皮生长因子受体-2染色较少。出生后第一周气管吸出液中胎盘生长因子蛋白的平均浓度为每IgA分泌成分单位0.64±0.42 pg/mL。出生后第一周内浓度稳定。较低的胎盘生长因子浓度与绒毛膜羊膜炎和乳糖基神经酰胺阳性相关。
血管内皮生长因子受体-2的染色模式似乎反映了不同内皮细胞的持续分化和活性。支气管肺发育不良患儿毛细血管内皮中血管内皮生长因子受体-2表达较低，可能反映了支气管肺发育不良所特有的血管发育失调。
