Impaired spreading of surfactant phospholipids in the lungs of newborn rats with pulmonary hypoplasia as a model of congenital diaphragmatic hernia induced by nitrofen.
In order to clarify the pathological outcome of congenital diaphragmatic hernia (CDH), we devised an animal model of CDH by administration of 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen) to pregnant rats, and determined the level and distribution of lung surfactant using the monoclonal antibody toward sphingomyelin and disaturated phosphatidylcholine (disat-PC). In control rats, the concentration of disat-PC was found to increase greatly from 16 to 18 days of gestation. Intragastric administration of nitrofen to pregnant rats at day 9 of gestation resulted in CDH in 42.7% of fetuses delivered after 20 days of gestation. In nitrofen-treated fetuses, the concentration of disat-PC in the lungs was lower than those in control fetuses, and surfactant apoprotein SP-A was similarly reduced in nitrofen-treated fetuses. However, the concentration of disat-PC in nitrofen-treated fetuses was higher than that in control fetuses at 18 days of gestation, indicating a synthetic potential of surfactant in nitrofen-treated fetuses comparable to that at the late stage of normal gestation. Immunohistochemical study with the antibody revealed that surfactant phospholipid was mainly in the form of intracellular granules in nitrofen-treated fetuses, probably causing the hypoplastic lungs and then CDH, in contrast to the uniform distribution on the pulmonary alveolar surface in control fetuses.
Department of Pediatrics, Kiyosenomori Hospital, Tokyo, Japan.
T
T
Utsuki
K
K
Hashizume
M
M
Iwamori
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001835:Body Weight; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D006540:Herbicides; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D007150:Immunohistochemistry; D008168:Lung / Q000002:abnormalities / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size; D010647:Phenyl Ethers; D010713:Phosphatidylcholines / Q000032:analysis; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013109:Sphingomyelins / Q000032:analysis
D006540:Herbicides; D010647:Phenyl Ethers; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D013109:Sphingomyelins; C017463:lecithins, disaturated; C007350:nitrofen