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VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

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Autor(es):
Sbragia, L. [1] ; Nassr, A. C. C. [2] ; Goncalves, F. L. L. [1] ; Schmidt, A. F. [3] ; Zuliani, C. C. [4] ; Garcia, P. V. [5] ; Gallindo, R. M. [1] ; Pereira, L. A. V. [5]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Div Cirurgia Pediat, Dept Cirurgia & Anat, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Fed Sao Carlos, Dept Hidrobiol, Ctr Ciencias Biol & Saude, BR-13560 Sao Carlos, SP - Brazil
[3] Cincinnati Childrens Hosp Med Ctr, Pediat House Off, Cincinnati, OH 45229 - USA
[4] Univ Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Campinas, SP - Brazil
[5] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Histol & Embriol, Campinas, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Brazilian Journal of Medical and Biological Research; v. 47, n. 2, p. 171-178, Fev. 2014.
Citações Web of Science: 13
Resumo

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression. (AU)