Montenegro M A, Palomino H
Department of Experimental Morphology, Faculty of Medicine, University of Chile, Santiago.
J Craniofac Genet Dev Biol. 1990;10(1):83-94.
The present study investigates the effects of several nonsteroidal anti-inflammatory drugs on mouse palatal fusion in vivo and in vitro. Five different nonsteroidal anti-inflammatory agents were injected into pregnant mice of the AKR-strain on day 13.5 of gestation. Paired palatal processes from 13.5- and 14.5-day-old mouse embryos were organ-cultured for 72 hours in control and anti-inflammatory drug-containing media. Each experimental group of animals and explants received one of the following drugs: naproxen, sulindac, indomethacin, diclofenac, and mefenamic acid. Drug treatment induced different frequencies of cleft palate in the offspring. The most teratogenic drug was sulindac, and indomethacin was almost ineffective. In vitro each drug prevented fusion of the palatine processes in treated explants, and the degree of inhibition was dependent on the stage of development at the time of explanation. In both the in vivo and in vitro experiments, the drugs prevented medial epithelial cell breakdown that normally occurs in the medial secondary palatal epithelium. The results obtained in the present study suggest that prostaglandins may play an important role in normal differentiation of the developing palatine region.
本研究调查了几种非甾体抗炎药在体内和体外对小鼠腭融合的影响。在妊娠第13.5天，将五种不同的非甾体抗炎药注射到AKR品系的怀孕小鼠体内。将13.5日龄和14.5日龄小鼠胚胎的成对腭突在对照培养基和含抗炎药的培养基中进行器官培养72小时。每组实验动物和外植体接受以下药物之一：萘普生、舒林酸、吲哚美辛、双氯芬酸和甲芬那酸。药物治疗导致后代出现不同频率的腭裂。致畸性最强的药物是舒林酸，而吲哚美辛几乎无效。在体外，每种药物都能阻止处理过的外植体中腭突的融合，抑制程度取决于解释时的发育阶段。在体内和体外实验中，这些药物都能阻止通常发生在腭中隔上皮的内侧上皮细胞解体。本研究获得的结果表明，前列腺素可能在发育中的腭区域的正常分化中起重要作用。
