Figueira R L, Gonçalves F L, Prado A R, Ribeiro M C, Costa K M, Silva O Castro E, Sbragia L
Laboratório de Cirurgia Fetal e Neonatal, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Laboratório de Transplante de Fígado, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2018 Oct 8;51(11):e7169. doi: 10.1590/1414-431X20187169.
Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P<0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P<0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia.
新生儿窒息是由于新生儿重要器官的氧气供应减少所致。长时间窒息后迅速恢复肺部氧气供应可导致肺损伤和呼吸功能下降，这是由诱导肺部血管变化的分子如一氧化氮（NO）和血管内皮生长因子（VEGF）的活性引起的。在本研究中，我们评估了接受新生儿窒息和机械通气模型的大鼠的肺和血管形态学、肺VEGF、VEGF受体（VEGFR-1/VEGFR-2）和内皮型一氧化氮合酶（eNOS）的表达。新生Sprague-Dawley大鼠（CEUA #043/2011）分为四组（每组n = 8）：对照组（C）、接受通气的对照组（CV）、缺氧组（H）和接受通气的缺氧组（HV）。胎儿在妊娠21.5天时收获。测量的形态学变量包括体重（BW）、肺总重量（TLW）、左肺重量（LLW）和TLW/BW比值。进行了肺血管测量、VEGFR-1、VEGFR-2、VEGF和eNOS免疫组织化学检测。形态学分析显示，与C组和H组相比，HV组的TLW和TLW/BW比值降低（P<0.005）。免疫组织化学显示，H组中VEGFR-2/VEGF增加，VEGFR-1表达降低（P<0.05），H组和HV组中eNOS表达较低。H组中中膜厚度增加，VEGFR-1、VEGFR-2、VEGF和eNOS的表达发生改变，尤其是在经历H组和HV组的新生儿中。这些数据表明，新生儿缺氧时存在由NO和VEGF信号介导的小动脉壁变化。
