Bannigan J G, Cottell D C
Department of Anatomy, Faculty of Medicine, University College, Dublin, Ireland.
Teratology. 1991 Aug;44(2):165-76. doi: 10.1002/tera.1420440204.
Clinical and laboratory observations show that denial of free communication between the amniotic fluid and lung fluid results in pulmonary hypoplasia. Thus, cleft palate resulting from tongue obstruction to palatal shelf elevation might be associated with disturbed lung development. This association exists in the Pena-Shokeir phenotype. The goal of these experiments was to see what effect bromodeoxyuridine (BUdR)-induced cleft palate had on lung development. LACA mice were injected with 500 mg/kg BUdR on E11 or E11 and E12 of gestation, a treatment known to produce a 25% and 50% incidence of cleft palate, respectively. BUdR had a direct retarding effect on lung growth but, when cleft palate occurred as well, the lungs were more severely affected. Morphometry showed that lungs from fetuses with cleft palate had only one-half the saccular volume of controls or of treated fetuses with normal palates. Although hypoplastic, lungs associated with cleft palate had type I and type II pneumocytes, and the latter were shown by electron microscopy to be capable of producing surfactant. Hence, cellular differentiation had not been affected by the treatment. Fetuses with cleft palate had less amniotic fluid than controls but significantly more than those with normal palates after treatment. Thus, the pattern of abnormalities in this animal model bears some resemblance to that of the human Pena-Shokeir phenotype.
临床和实验室观察表明，羊水与肺液之间的自由交流受阻会导致肺发育不全。因此，因舌阻碍腭板抬高而导致的腭裂可能与肺发育紊乱有关。这种关联存在于佩纳-绍凯尔综合征（Pena-Shokeir phenotype）中。这些实验的目的是观察溴脱氧尿苷（BUdR）诱导的腭裂对肺发育有何影响。在妊娠第11天或妊娠第11天和第12天给LACA小鼠注射500mg/kg的BUdR，已知这种处理分别会导致25%和50%的腭裂发生率。BUdR对肺生长有直接的抑制作用，但是当同时发生腭裂时，肺受到的影响更严重。形态学测量显示，腭裂胎儿的肺囊泡体积只有对照组或腭正常的经处理胎儿的一半。尽管发育不全，但与腭裂相关的肺有I型和II型肺上皮细胞，电子显微镜显示后者能够产生表面活性物质。因此，细胞分化未受该处理影响。腭裂胎儿的羊水比对照组少，但处理后明显比腭正常的胎儿多。因此，这个动物模型中的异常模式与人类佩纳-绍凯尔综合征有一些相似之处。
