邻苯二甲酸二丁酯阻断Shh信号通路导致尿道下裂的作用机制  

The mechanisms of hypospadiac male fetal rats induced by di-n-butyl phthalate (DBP) inhibition of Shh signaling in genital tubercle

作　　者：徐进宇[1] 张炜[2] 马隆[2] 蒋君涛[3] 吴婷[2] 

机构地区：[1]南京医科大学附属无锡第一人民医院泌尿外科,无锡214002 [2]南京医科大学第一附属医院泌尿外科 [3]上海交通大学附属第一人民医院泌尿外科

出　　处：《江苏医药》2007年第11期1135-1137,共3页Jiangsu Medical Journal

基　　金：国家973计划课题资助项目(2002CB512908;2001CCA04900)

摘　　要：目的研究邻苯二甲酸二丁酯（DBP）孕晚期染毒诱导雄性胎鼠发生尿道下裂的作用机制。方法雌鼠怀孕（GD）第14～18天,实验组和对照组分别予DBP750mg/kg、大豆油灌胃。在GD19d,解剖孕鼠取出胎鼠,鉴别出实验组中发生尿道下裂和未发生尿道下裂的雄性胎鼠及对照组中的雄性胎鼠,分为尿道下裂组、非尿道下裂组和对照组。用实时定量逆转录聚合酶链反应方法检测胎鼠生殖结节（GT）中Shh（sonic hedgehog）和骨形态发生蛋白4（Bmp4）mRNA相对表达水平。结果尿道下裂组、非尿道下裂组和对照组Shh mRNA相对表达水平分别为0.27±0.13、0.66±0.41和0.85±0.19,Bmp4 mRNA相对表达水平分别为0.18±0.05、0.40±0.25和1.00±0.44。Shh mRNA在尿道下裂组的表达较非尿道下裂组和对照组降低（P〈0.05）,Bmp4 mRNA在尿道下裂组和非尿道下裂组的表达较对照组降低（P〈0.05）。结论DBP通过对GT生长发育早期Shh信号系统中部分作用因子发生作用而影响GT的生长发育,导致尿道下裂的发生。Objective To investigate the mechanisms of hypospadiac male fetal rats induced by di-n-butyl phthalate （DBP） during late gestation. Methods Timed pregnant rats were given DBP by gastric intubation at a dose of 0 （control group） or 750 mg/kg （experimental group） from gestation day （GD） 14 to 18. On GD 19, male fetal rats were allocated to three groups： hyposadias group, nonhyposadias group and control group after identifying hypospadiac and nonhyposadiac male offspring from experimental group and control male offspring from control group. RT-PCR was used to quantify relative mRNA expression levels on GD 19 for sonic hedgehog （Shh） and bone morphogenetic protein 4 （Bmp4）in rat＇s genital tubercle （GT） of above three groups. Results Relative mRNA expression levels for Shh from hyposadias group, nonhyposadias group and control group were 0. 27 ± 0.13, 0.66 ± 0.41 and 0. 85 ± 0. 19, respectively. Relative mRNA expression levels for Bmp4 from above three groups were 0.18±0.05, 0.40± 0.25 and 1.00± 0.44, respectively. Shh mRNA expression in rat＇s GT from hypospdias group was significantly decreased compared with that from nonhypospadias and control groups （P〈0.05）. Bmp4 mRNA expression in rat＇s GT from hypospdias and nonhypospadias groups was significantly decreased compared with that from control group （P〈0.05）. Conclusion DBP affects the development of GT by regulating partial factors of Shh signaling in early development of GT, inducing the occurrence of hypospadias in male offspring.

关 键 词：邻苯二甲酸二丁酯 尿道下裂 生殖结节 Shh信号系统 

分 类 号：R691[医药卫生—泌尿科学]