邻苯二甲酸二(2-乙基)己酯诱导大鼠尿道下裂及对阴茎TGF-β1、TGF-βR3表达的影响  

Di(2-ethylhexyl)phthalate Induces Hypospadias in Rat and Its Effecton the Expression of TGF-b1,TGF-bR3 in Genital Tubercles

作　　者：陈柏林[1] 刘星[1] 吴盛德[1] 袁心刚[1] 何昀[1] 徐明灯[1] 刘东尧[1] 温晟[1] 魏光辉[1] 

机构地区：[1]重庆医科大学附属儿童医院泌尿外科,儿童发育疾病研究省部共建教育部重点实验室,重庆400014

出　　处：《生殖与避孕》2011年第2期88-92,101,共6页Reproduction and Contraception

基　　金：科技部十一五科技支撑计划(No.2006BAI05A06);高等学校博士学科点专项科研基金(No.200806310005)项目

摘　　要：目的:探讨诱导建立大鼠先天性尿道下裂,研究邻苯二甲酸二(2-乙基)己酯(DEHP)及胎鼠阴茎内转化生长因子(TGF-β1,TGF-βR3)在尿道下裂发生机制中的意义。方法:SD孕鼠随机分为DEHP组(每日500 mg/kg)和大豆油对照组,每组20只。分别于母鼠孕12 d至19 d(GDl2～19)持续经口灌注给药。每组分别留取10只孕鼠让其正常分娩,出生第1日计数新生大鼠,并在解剖显微镜下测量雄性新生鼠的肛门生殖器距离(AGD)和称体质量;雄性仔鼠70日龄时逐个检查尿道下裂的发生情况。另10只孕鼠于孕第19日行剖宫产取仔鼠,应用逆转录-聚合酶链反应(RT-PCR)的方法检测胎鼠阴茎TGF-β1、TGF-βR3 mRNA的表达水平。结果:DEHP成功诱导出尿道下裂大鼠动物模型,DEHP组仔鼠体质量及AGD较对照组明显缩小(P<0.05)。DEHP组胎鼠阴茎TGF-β1、TGF-βR3 mRNA表达水平增加(P<0.05)。结论:DEHP成功诱导建立先天性尿道下裂大鼠模型,胎鼠阴茎内TGF-β1、TGF-βR3异常表达可能是尿道下裂的发生机制之一。Objective：To induce hypospadias in rat with di（2-ethylhexyl） phthalate（DEHP）,andinvestigate the expression of TGF-b1,TGF-bR3 in fetal rat genital tubercles.Methods：Pregnant SD rats wererandomly divided into 2 groups with 20 in each group：DEHP（500 mg/kg） group and the control.Rats weregavaged from gestation day 12 to 19（GDl2-19）.Ten pregnant rats were let to delivery normally in each group.After the pregnant rats had delivered,the male offsprings were counted and the anal genital distance（AGD）and body weight were measured.Hypospadias were also observed after postnatal 70 d of the male offspring.Fetal rats were harvested at GDl9 in the remaining pregnant rat.Semi-quantitive RT-PCR was used to measuremRNA of TGF-b1 and TGF-bR3 expression in rat genital tubercles of above two groups on GD19.Results：Hypospsdias was induced in male rat.The AGD and body weight in DEHP group were significantlyshorter than those in the control（P0.05）.The levels of TGF-b1 and TGF-bR3 mRNA were up-regulated inexperimental group（P0.05）.Conclusion：Murine model of hypospadias has been established successfully bytreatment with DEHP,and up-regulated TGF-b1 and TGF-bR3 in early development of genital tubercles maybe one of the pathogenesis of hypospadias.

关 键 词：邻苯二甲酸二(2-乙基)己酯 尿道下裂 TGF-Β1 TGF-βR3 

分 类 号：R994.6[医药卫生—毒理学]