小鼠尿道下裂动物模型的建立

目的 :采用抗雄激素类药物氟他胺诱导建立小鼠尿道下裂动物模型 ,为进一步研究尿道下裂发病的分子作用机制和治疗提供理论和试验依据。　方法 :80只 6～ 8周龄ICR孕小鼠 ,体重 2 8～ 30 g ,随机分成 4组 ,每组 2 0只。在孕 12～ 16d时连续 5d皮下分别注射氟他胺 0 (A组 )、2 5 (B组 )、5 0 (C组 )、10 0 (D组 )mg·kg-1·d-1,出生后每组 2只母鼠的雄性仔鼠解剖观察睾丸位置、前列腺发育情况 ,出生后 4周观察有无尿道下裂、隐睾和前列腺发育情况。　结果 :A～D组子一代尿道下裂发生率分别为 0、4 4 .2 %、92 .7%、10 0 % ;隐睾发生率分别为 0、4 .8%、2 3.2 %、32 .4 %。C和D组前列腺均不发育 ,B、C和D组肛门至尿生殖结的距离均缩短。　结论 :用氟他胺可以诱导出稳定的雄性小鼠尿道下裂模型 ,适宜推广。

A Mouse Model of Hypospadias Induced by Flutamide

OBJECTIVE: To establish a mouse model of hypospadias induced by flutamide to further studying molecular mechanisms of hypospadias etiology. METHODS: Eighty timed pregnant ICR mice were randomly divided into four groups. Flutamide was injected subcutaneously (s.c.) with mixture sesame oil at 0 (Group A), 25 (Group B), 50 (Group C), 100 (Group D) mg.kg-1.d-1 from GD (gestation days) 12 to 16, respectively. The fetuses of two pregnants from each group were anatomized to observe the position of testes and the development of prostates on the day of delivery. Urethras and the position of testes were examined on postnatal day 28. RESULTS: Hypospadias was seen in Group A (0), B (44.2%), C (92.7%) and D (100%), and cryptorchidism in Group A (0), B (4.8%), C (23.2%) and D (32.4%), respectively. Flutamide caused 100% incidence of prostate agenesis in Group C and D and 19.2% in Group B, and 100% incidence of female-like anogenital distance in Group B, C, and D. CONCLUSION: The experimental model of hypospadias induced by flutamide is steadier and more suitable for popularization.