氟他胺建立SD大鼠尿道下裂模型的实验研究

The establishment of hypospadias rat model with flutamide

目的采用抗雄激素类药物氟他胺诱导建立大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实验依据。方法孕鼠20只,随机分成2组:生理盐水(normal saline,NS)对照组和氟他胺(Flutamide,Flu)组,每组10只。在孕12～17d时连续6d分别经皮下注射等量生理盐水或用生理盐水配制的氟他胺溶液(12.5mg.kg-1.d-1)。于孕18d解剖两只母鼠,提取雄性胎鼠生殖结节做病理切片,同时观察睾丸位置和前列腺发育情况。待孕鼠分娩完毕,即对仔鼠进行记数,并于出生后第2、13、28天测量肛门生殖器距离(anogenital distance,AGD)和称重;观察每组雄性仔鼠的尿道口和睾丸位置、乳晕数量及拍照。结果与对照组相比,氟他胺组雄性子代大鼠尿道下裂畸形发生率为100%,单侧隐睾发生率为31.25%,解剖观察无前列腺,出现乳晕数均为12个,AGD较对照组明显缩短,有显著统计学差异,但体重随着时间的推移无明显变化。结论用氟他胺可以诱导出稳定、直观的雄性大鼠尿道下裂模型,适宜推广。

Objective To establish a rat model of hypospadias by flutamide to further studying molecular mechanisms of hypospadias etiology . Methods Twenty pregnant SD rats were divided randomly into 2 groups. Hut amlde was injected subcutaneously （sc） with NS at doses of 12.5mg·kg^-1·d^-1 from GD （gestation days）12 to 17, and in control group with tales doses NS. The fetuses of two pregnants from each group were anatomized to extract genital tubereh to make pathological section and observe the position of testes and the development of prostates on GD18 .The position of Urethral opening and testes were examined on postnatal day （PND） 13 and 28 . Results The 100% incidence of hypospadias and 31.25% incidence of single crypterchidism were seen in Flu group. Flutamide caused 100% incidence of prostate agenesis ,100% incidence of female-like arecla of nipple ,and 100% incidence of female-like anogenital distance（ACD） .Conclusions The experimental model of hypospadias induced by flutamide is steadier and more suitable for popularization.