Notch1在邻苯二甲酸二丁酯致大鼠尿道下裂发生中的表达  

Expression of Notch1 in the genital tubercle of male rats with hypospadias induced by Di-n-butyl phthalate

作　　者：周耀军[1] 魏俊峰[1] 张力峰[1] 王勇[1] 张炜[1] 

机构地区：[1]南京医科大学第一附属医院泌尿外科,江苏南京210029

出　　处：《中华男科学杂志》2012年第3期222-226,共5页National Journal of Andrology

基　　金：国家自然科学基金(30872596)~~

摘　　要：目的:利用邻苯二甲酸二丁酯(DBP)胚胎期暴露诱导子代SD大鼠发生尿道下裂,检测Notch1在尿道下裂胎鼠与正常胎鼠生殖结节(GT)中的差异表达,探讨其在DBP致大鼠尿道下裂发生中的作用。方法:SD孕鼠20只,随机分为两组,实验组和对照组各10只。妊娠(GD)14～18 d,实验组和对照组分别给予DBP 800 mg/(kg.d)和大豆油2 ml/(kg.d)灌胃,孕第19天剖宫产后记录雄性胎鼠出生体重(BW)、肛门和生殖器之间的距离(AGD)及尿道下裂发生率。取DBP组中发生尿道下裂的雄性胎鼠和对照组中的雄性胎鼠,分为尿道下裂组与对照组,提取生殖结节,用Western印迹法和免疫组化法分析Notch1的表达。结果:实验组子代雄性胎鼠体重为(4.40±0.30)g,对照组为(6.11±0.40)g,实验组较对照组明显下降(P<0.05);实验组AGD为(2.17±0.18)mm,对照组为(3.28±0.16)mm,实验组较对照组明显缩短(P<0.05),尿道下裂发生率为42.9%。Notch1在尿道下裂组的相对表达量为0.671±0.021,正常对照组为1.327±0.031,差异有统计学意义(P<0.05);Notch1主要定位于生殖结节上皮细胞,尿道下裂组染色强度明显弱于对照组。结论:染毒期间DBP对雄性子鼠有明显毒性作用,改变了生殖结节中Notch1的表达,可能影响细胞的增殖和凋亡及上皮-间质转化(EMT),导致尿道下裂的发生。Objective ： To detect the differential expression of Notchl in the genital tubercle （GT） of fetal male rats with hypospadias induced by maternal exposure to Di-n-butyl phthalate （DBP） and that in normal control fetal rats in order to further explore the role of Notehl in DBP-indueed hypospadias. Methods ： Twenty pregnant SD rats were equally and randomly divided into an experimental and a control group, the former given DBP and the latter soybean oil intragastrically at 800 mg/（ kg·d） and 2 ml/d respectively from gestation day （GD） 14 to GD 18. On GD 19, the birth weight （BW）, anogenital distance （AGD） and hypospadias incidence were recorded, GTs of the fetal male rats collected, and the expression of Notchl analyzed by Western blot and immunohistochemistry. Results ： The BW of the fetal male rats was （4.40 ± 0.30 ） g in the experimental group, significantly lower than （ 6.11 ± 0.40 ） g in the control （P 〈 0.05 ）, and the AGD was （2.17 ± 0.18 ）mm in the former, markedly shorter than （3.28 ± 0.16） rnm in the latter （P 〈 0.05）. The incidence of hypospadias was 42.9%. The relative expression of Notehl was remarkably lower in the hypospadiac rats than in the normal controls （0. 671 ±0.021 vs 1. 327 ±0. 031, P 〈0.05）, and it was mainly located in the epithelial cells of the GT. The staining intensity was obviously weaker in the hypospadias than in the normal control group. Conclusion ： DBP has an obvious toxic effect on fetal male rats and can change the expression of Notchl in the GT. It possibly affects cell proliferation and apoptosis and epithelial-to-mesenchymal transition （EMT）, resulting in the occurrence of hypospadias. Natl J Androl, 2012, 18 （3） ： 222 - 226

关 键 词：NOTCH1 邻苯二甲酸二丁酯 尿道下裂 生殖结节 

分 类 号：R695[医药卫生—泌尿科学]