Utsuki T, Hashizume K, Iwamori M
Department of Pediatrics, Kiyosenomori Hospital, Tokyo, Japan.
Biochim Biophys Acta. 2001 Mar 30;1531(1-2):90-8. doi: 10.1016/s1388-1981(01)00087-7.
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.
为了阐明先天性膈疝（CDH）的病理结果，我们通过给怀孕大鼠施用2,4 - 二氯苯基 - 对硝基苯基醚（硝呋烯腙）设计了一种CDH动物模型，并使用针对鞘磷脂和二饱和磷脂酰胆碱（二饱和PC）的单克隆抗体来测定肺表面活性剂的水平和分布。在对照大鼠中，发现二饱和PC的浓度在妊娠16至18天大幅增加。在妊娠第9天给怀孕大鼠胃内施用硝呋烯腙，导致在妊娠20天后分娩的胎儿中有42.7%出现CDH。在经硝呋烯腙处理的胎儿中，肺中二饱和PC的浓度低于对照胎儿，并且表面活性剂载脂蛋白SP - A在经硝呋烯腙处理的胎儿中也同样减少。然而，在妊娠18天时，经硝呋烯腙处理的胎儿中二饱和PC的浓度高于对照胎儿，这表明经硝呋烯腙处理的胎儿中表面活性剂的合成潜力与正常妊娠后期相当。用该抗体进行的免疫组织化学研究表明，与对照胎儿中肺泡表面的均匀分布相比，在经硝呋烯腙处理的胎儿中，表面活性剂磷脂主要以细胞内颗粒的形式存在，这可能导致肺发育不全进而导致CDH。
