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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。
Objective To explore the congenital hypodermic model of male pups through artificial intervention of androgen receptor in pregnant maternal rats to explore the optimal dosage time and dosage for the modeling. Methods Kunming mice were administrated with Flutamide by intragastric administration from the 15th day after conception, and were administered continuously for 5 days. The doses were 66.7mg, 133.3mg, 200.0mg, 266.7mg and 333.3mg / kg, respectively. To be their natural childbirth, in the pups were born 21d after observation male male external genital protrusion morphological changes. Results The male genitalia of 133.3mg / kg and below dose groups had no obvious abnormalities. The male genitalia of 200.0mg dose group had obvious dehiscence at the top of the genital process and the rate of deformity was 86.6%. The male genitalia of 266.7gm / kg dose Very similar to female mice, hair scrotum Department, testicular no exception, was cryptorchidism. The deformity rate reached 83.3%. In the 333.3mg / kg dose group, the external genital protrusion of the male mice completely split back and formed a vaginal structure on the anal side. Conclusions Kunming mice were given intragastric administration of 266.7mg / kg ~ 333.3mg / kg of fluorobutylamide starting from the 15th day after conception, and the continuous administration for 5 days resulted in more than 80% congenital hypospadias in male pups.