Effect of hyperoxia on surfactant protein gene expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.
The hypoplastic lung in congenital diaphragmatic hernia (CDH) has both a quantitative and qualitative reduction in surfactant. Recently, the role of oxygen (O2) as a regulator of pulmonary surfactant-associated protein (SP) gene expression has been reported. The mRNA level of SP has been demonstrated to be increased in the lungs of animals exposed to hyperoxia. The aim of this study was to investigate SP mRNA expression in hypoplastic CDH lung in rats during mechanical ventilation in order to determine the effect of O2 on SP synthesis in CDH. A CDH model was induced in pregnant rats following administration of nitrofen. The newborn rats with CDH and controls were intubated and ventilated. Ventilation was continued for 6 h under 100% oxygen. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of mRNA expression of SP-A, SP-B, SP-C, and SP-D. Relative amounts of SP-A, SP-B, and SP-D mRNA expression in CDH lung were significantly decreased compared to controls at birth and 6 h after ventilation. There was no significant difference in SP-C mRNA expression between CDH animals and controls. Upregulated mRNA expression of SP-A, SP-B, and SP-D in lungs of control animals at 6 h after ventilation suggests that oxygenation accelerates postnatal SP synthesis in normal lungs. The inability of O2 to increase SP mRNA expression in hypoplastic CDH lung suggests that the hypoplastic lung is not responsive to increased oxygenation for the synthesis of SP.
Shima
H
H
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Guarino
N
N
Puri
P
P
D000014:Abnormalities, Drug-Induced / Q000378:metabolism*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis; D006548:Hernia, Diaphragmatic / Q000378:metabolism*; D065630:Hernias, Diaphragmatic, Congenital; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities / Q000378:metabolism*; D008297:Male; D010575:Pesticides / Q000009:adverse effects; D010647:Phenyl Ethers / Q000009:adverse effects; D011247:Pregnancy; D011510:Proteolipids / Q000096:biosynthesis; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006023:Glycoproteins; D010575:Pesticides; D010647:Phenyl Ethers; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C007350:nitrofen