有机磷农药-敌敌畏诱导建立大鼠尿道下裂模型的实验研究  

Organophosphorous pesticide dichlorvos induces hypospadias in rat

作　　者：龚春雨[1] 黄鲁刚[2] 胡渝华[3] 李虹[1] 李响[1] 陈绍基[2] 

机构地区：[1]四川大学华西医院泌尿外科,成都610041 [2]四川大学华西医院小儿外科,成都610041 [3]四川大学公共卫生学院生殖毒理教研室

出　　处：《中华小儿外科杂志》2005年第10期544-547,共4页Chinese Journal of Pediatric Surgery

基　　金：四川省应用基础研究项目(03JY029-073-2)

摘　　要：目的尝试用有机磷农药-敌敌畏建立尿道下裂大鼠模型,敌敌畏与尿道下裂发生的关系.方法40只孕鼠,分成3组:生理盐水对照组(CG)10只;敌敌畏高剂量组10只;敌敌畏低剂量组20只.在大鼠怀孕12～17 d期间,每组每天分别给予管喂生理盐水1.5～2 ml/d,敌敌畏20 mg·kg-1·d,敌敌畏10 mg·kg-1·d-1.待孕大鼠分娩完毕,即对新生大鼠点数并在普通放大镜及解剖显微镜下观察雄性新生鼠的阴茎包皮外观、尿道口位置、称体重和测量肛生殖距离(AGD).结果敌敌畏高、低剂量组均诱导出了大鼠尿道下裂,两组间发生率无统计学差异(P＞0.05),对照组大鼠的生殖器未见异常改变;各组新生大鼠的AGD、体重比较有统计学差异(P＜0.05).敌敌畏可使新生大鼠的AGD明显缩短,体重明显减轻,并显示与敌敌畏有剂量依赖关系.结论①用有机磷农药-敌敌畏成功建立的尿道下裂大鼠模型可为研究尿道下裂病因学和预防干预措施提供进一步研究的基础;②首次采用有机磷类农药诱导出大鼠尿道下裂畸形,同时有缩短AGD和减轻新生大鼠体重的作用,从实验动物学角度支持了流行病学的研究发现,有机磷农药可能作为一种环境内分泌干扰物质,是尿道下裂发病率增加的原因之一.Objective Organophosphorous dichlorvos is a widely used pesticide. We established a dichlorvos induced hypospadias model in rat. Methods 40 time-pregnant rats were divided into 3 groups： 10 in saline control group （CG）, 10 in dichlorvos 20 mg·kg^-1 ·d^-1 group, and 20 in dichlorvos 10 mg·kg^-1·d^-1 group. Between E12 and E17, rats were gavaged with 1.5 ml～2 ml saline, 20 mg· kg^-1 ·d^-1 dichlorvos, 10 mg·kg^-1·d^-1 dichlorvos respectively. After birth, the male newborn rats were examined for the penis appearance, urethral orifice position of the newborn rats and micturition with magnifying lens and anatomic microscope. Results Dichlorvos groups induced hypospadias of newborn rats. There was no statistic difference in the incidence of hypospadias between the diehlorvos groups of different dosage; There is differences between groups in their AGD and body weight（P〉0. 05）. Dichlorvos can shorten the AGD and reduces the weight of newborn rats. Moreover the severity is dose-dependent. Conclusions We have established a rat hypospadias model for further research in etiology and therapy; It was discovered the first time that dichlorvos can induce the hypospadias rats. Diehlorvos shortens AGD and reduces the weight of newborn rats. The organphosphorus pesticide may be an environment teratogenic substance, causing hypospadias in human.

关 键 词：杀虫药 有机磷 敌敌畏 尿道下裂 动物实验替代试验 有机磷农药 大鼠模型 实验研究 内分泌干扰物质 统计学差异 大鼠体重 

分 类 号：R-332[医药卫生]