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Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia

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World Journal of Pediatrics 2014年第4期10卷 354-359页

作者： María de Lourdes Lemus-Varela amed soliz Belinda Claudia Gómez-Meda Ana Lourdes Zamora-Perez José Manuel Ornelas-Aguirre Valery Melnikov Blanca Miriam Torres-Mendoza Guillermo Moisés Zúñiga-González Division of Neonatology High Specialty Medical UnitPediatric HospitalWestern National Medical CenterMexican Social Security InstituteGuadalajaraJaliscoMéxico Neonatal Intensive Care Unit Division of NeonatologyMiami Children's HospitalMiami FLDUSA Molecular Biology in Medicine Institute Molecular Biology and Genomic DepartmentHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Odontology Research Institute Integrated Odontology Clinic DepartmentHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Pathology Department High Specialty Medical UnitNorth-western National Medical CenterMexican Social Security InstituteCiudad ObregónSonoraMéxico School of Medicine University of ColimaColimaMéxico Division of Neurosciences Western Biomedical Research CenterMexican Social Security Institute and Department of ClinicsHealth Sciences University CenterUniversity of GuadalajaraGuadalajaraJaliscoMéxico Mutagenesis Laboratory Western Biomedical Research CenterMexican Social Security InstituteGuadalajaraJaliscoMéxico

Background:Lung hypoplasia,pulmonary persistent hypertension of the newborn and its morphological changes are the main features in congenital diaphragmatic hernia(CDH).This study was undertaken to investigate if antenatal use of sildenafil and/or bosentan attenuates vascular remodeling,promotes branching,and improves alveolarization in experimental nitrofeninduced ***:Nitrofen(100 mg)was gavage-fed to pregnant rats at post conception day(PCD)9 to induce *** rats were randomized to 5 groups:1)control;2)nitrofen;3)nitrofen+sildenafil 100 mg/kg per day at PCD 16-20;4)nitrofen+bosentan 30 mg/kg per day,at PCD 16-20,and 5)nitrofen+bosentan+sildenafil,same doses and administration *** cesarean delivery,the offsprings were sacrifi *** diaphragmatic defect and pulmonary hypoplasia were identified,and the lungs were *** wall thickness,bronchiolar density and alveolarization were ***:The offsprings with CDH were characterized by severe pulmonary hypoplasia(lung weight-to-body weight ratio:0.0263[95%confidence interval(CI)0.0242-0.0278)]in the nitrofen group versus 0.0385(95%CI 0.0355-0.0424)in the control group(P=0.0001).Pulmonary arterial wall thickness was decreased to 3.0(95%CI 2.8-3.7)μm in the nitrofen+sildenafil group versus 5.0(95%CI 4.1-4.9)μm in the nitrofen group(P=0.02).Terminal bronchioles increased to 13.7(95%CI 10.7-15.2)μm in the nitrofen+bosentan group in contrast to 8.7(95%CI 7.2-9.4)μm in the nitrofen group(P=0.002).More significant differences(P=0.0001)were seen in terminal bronchioles in the nitrofen+sildenafil+bosentan group than in the nitrofen group[14.0(95%CI 12.5-15.4)μm versus 8.5(95%CI 7.1-9.3)μm].Pulmonary arterial wall thickness was also decreased in the former ***:In this rat model,antenatal treatment with sildenafil attenuates vascular *** promotes the development of terminal bronchioles in nitrofen-induced CDH.

关键词： antenatal treatment bosentan congenital diaphragmatic hernia pulmonary hypoplasia sildenafil

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