Journal
PEDIATRIC SURGERY INTERNATIONAL
Volume 32, Issue 6, Pages 591-598Publisher
SPRINGER
DOI: 10.1007/s00383-016-3886-1
Keywords
Congenital diaphragmatic hernia; Retinoic acid; Tracheal occlusion; Rat model; Nitrofen
Categories
Funding
- FAPESP-Sao Paulo Research Foundation [2008/50347-9, 2011/00794-1, 2008/52772-9, 2011/12587-0, 2014/02519-6]
- CNPq-Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [302433/2014-7]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/12587-0, 14/02519-6] Funding Source: FAPESP
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To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH). Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2). Compared to control animals, CDH had increased MWT (44 +/- 15 vs. 58 +/- 7; p < 0.05) and decreased expression of VEGF, VEGFR1, and VEGFR2 (p < 0.05). Treatment with RA or TO alone, and RA + TO reduced the MWT (46 +/- 9, 42 +/- 11, 46 +/- 8, respectively) and improved the expression of VEGF, VEGFR1, and VEGFR2 compared to CDH (p < 0.05). However, the combination of RA + TO did not confer additional benefit in the reduction of the MWT or in increasing the VEGF and its receptors compared to either treatment alone. Antenatal treatment with either RA or TO improved the MWT and expression of VEGF and its receptors in a CDH rat model. However, combined treatment with RA + TO was not superior to either treatment alone.
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