Abstract: Objective Through artificially interfering the pregnant mice's androgen receptors to make their male whelps suffer congenital hypospadias, and to optimize the conditions for medication time and dosage. Methods\ Female mice (Kunming species), from the 15th day of their pregnancy, received garage of fiutamide for 5 days in a dosage of 66.7mg, 133.3mg, 200.0mg,266.7mg, or 333.3mg/kg; after withdrawal, the pregnant mice ran a spontaneous labour; from on the 21st day after birth the male whelps were observed on the morphological change of their external genital processes. Results\ Group with a dosage of 133.3mg/kg or under it showed no marked abnormality in their external genital processes; group with 200.0mg/kg showed an obvious cleft occurred in the top of genital processes, with a deformity rate up to 86.6%; group with 266.7mg/kg showed their external genitals were very much similar to the female mice's, with pubes around scrotum, testes unprotruded and cryptorehid; deformity rate up to 83.3%; group with 333.3mg/kg showed a complete crack backwards in the external genitals, and even a vagina_like orifice formed in the anal side. Conclusion\ Using female mice (Kunming species), from the 15th day of their pregnancy, given a flutamide gavage in a dosage of 266.7mg/kg~333.3mg/kg for consecutive 5days may make 80% or over of congenital hypospadias models among the male mouse whelps in the experiment.

Key words: Congenital hypospadias, Mice, Kunming, Flutamide

摘要： 目的通过人工干预怀孕母鼠体内雄激素受体,造成雄性幼鼠先天性尿道下裂模型,探索造模所需的最佳给药时间及剂量。方法昆明种小鼠,从受孕后第15d开始灌胃给予氟丁酰胺(Flutamide),连续给药5d,剂量分别为66.7mg、133.3mg、200.0mg、266.7mg及333.3mg/kg,停药后待其自然分娩,于仔鼠出生后第21d观察雄性幼鼠外生殖器突起的形态变化。结果133.3mg/kg及以下剂量组雄性幼鼠外生殖器无明显异常;200.0mg剂量组雄性小鼠外生殖器突起顶部发生明显裂口,畸形率达86.6%;266.7gm/kg剂量组雄性小鼠外生殖器与雌性小鼠非常相似,阴囊部生毛,睾丸不外突,呈隐睾状。畸形率达到83.3%;333.3mg/kg剂量组雄性小鼠外生殖器突起向后完全裂开,在肛门侧形成一个类似阴道的结构。结论昆明种小鼠从受孕后第15d开始灌胃给予266.7mg/kg~333.3mg/kg氟丁酰胺,连续给药5d,可造成80%以上的雄性幼鼠先天性尿道下裂模型。

关键词: 先天性尿道下裂, 昆明小鼠, 氟丁酰胺