尿道下裂大鼠模型的建立及莠去津对大鼠尿道下裂发病率的影响

The establishment of hypospadias rat model and embryoteratogenic test of Atrazine

目的建立SD大鼠尿道下裂动物模型,探讨莠去津对大鼠尿道下裂的发病率有无影响。方法将受孕的SD大鼠120只,随机分为6组,每组20只。于孕期第11～16天时,每天分别给予莠去津25mg/kg、莠去津100mg/kg、莠去津200mg/kg、植物油1ml/kg、非那雄胺10mg/kg、非那雄胺20mg/kg。给药后即刻观察并记录动物的反应情况,于孕期第0、3、6、9、12、15、18、20天称重以调整剂量。于仔鼠出生后第21天,检测其有无尿道下裂,并记录其肛生殖窦距离及其体重。结果200mg/kg莠去津组、10mg/kg非那雄胺组、20mg/kg非那雄胺组仔鼠出生时尿道下裂发生率分别为10.23%、28.30%、67.03%;25mg/kg莠去津组中有2只母鼠的胚胎着床后发育停滞。各组雄性仔鼠的肛生殖窦距离（AGD）与其体重存在正相关关系。结论①大鼠仔鼠尿道下裂表现为阴茎头和（或）阴茎腹侧裂开、尿道口异位,并有肛生殖窦距离的变窄,SD大鼠孕期第11～16天管饲每天10mg/kg及20mg/kg非那雄胺,可以建立尿道下裂动物模型。②莠去津对SD大鼠是一种胚胎致畸物。

Objective To establish an easily reproducible animal model of hypospadias and to test whetherAtrazine can induce hypospadias in animal experiment. Methods From the llth to 16th day after conception,120 conceived SD rats were divided randomly into 6 groups： one coin oil group（1 ml/kg/d）, two finasteride groups（10mglkg/d, 20 mg/kg/d）, three Atrazine groups（25 mg/kg/d, 100 mglkgld, 200 mg/kg/d）. When all pregnant rats had delivered, the new born rats were counted and the penis appearance, urethal orifice position and micturation were observed with magnifying lens and anatomy microscope. Results Hypospadias were found in new born male rats treated prenatally with Finasteride （ 10 mg/kg/d, 20 mg/kg/d） and 200 mg/kg/ d Atrazine groups. The incidence was 28.30%, 67.03% , 10.23% respectively. Embryotoxic effects were observed at 25 mg/kg/d Atrazine group in 2 rats and associated with no severe maternal toxicity. Conclusions ①A hypospadias SD rats model can be established by Finasteride and it is easily reproducible. ②The Atrazine was teratogenic to the SD rats, embryotoxic effects were observed at the low dose level and associated with no severe maternal toxicity.