Wnt/β-catenin与NF-κB信号通路在邻苯二甲酸二丁酯诱导雄性大鼠发生尿道下裂中的表达  

Expression of Wnt /β-catenin and NF-κB pathway in genital tubercle of hypospadiac male rats with utero exposure to di-n-butyl phthalate

作　　者：张力峰[1] 王勇[1] 常俊锴[1] 魏俊峰[1] 魏云飞[1] 秦超[1] 冯宁翰[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：《南京医科大学学报（自然科学版）》2010年第11期1533-1536,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金面上项目(30872596)

摘　　要：目的:利用邻苯二甲酸二丁酯(DBP)孕晚期暴露诱导子代SD大鼠发生尿道下裂,验证Wnt/β-连环蛋白(β-catenin)及核因子κB(NF-κB)信号通路中关键蛋白在胎鼠生殖结节中的差异表达,探讨该通路在DBP致大鼠生殖系统发育异常过程中的作用机制。方法:孕SD大鼠20只,随机分为DBP组和对照组,在妊娠(GD)14～18天,每天分别通过灌胃给予DBP和大豆油800mg/kg,于GD19天处死后取胎鼠,鉴别出DBP组中发生尿道下裂的雄性胎鼠及对照组中的雄性胎鼠,分为尿道下裂组与正常对照组,提取生殖结节组织,Westernblot检测β-catenin、糖原合成酶-3β(GSK-3β)和NF-κB的表达情况。结果:DBP染毒后子代雄性胎鼠出生体重较对照组明显下降,肛门生殖器距离(AGD)明显缩短,尿道下裂发生率为46.7%,同时尿道下裂组与正常对照组中β-catenin相对表达量的比值为0.505±0.014(P<0.05),GSK-3β与NF-κB相对表达量的比值分别为1.903±0.018和3.661±0.021(P均<0.05)。结论:DBP可能通过干预生殖结节中Wnt/β-catenin和NF-κB信号通路的正常表达导致尿道下裂的发生。Objective：To evaluate the expression of Wnt /β-catenin and NF-κB pathway in hypopspadiac male rats treated by utero exposure to di-n-butyl phthalate（DBP）.Methods：Twenty pregnant rats were randomly divided into two groups,and treated group was given DBP by gastric intubation at a dose of 800 mg /kg from gestation day （GD） 14 to GD18.On GD19,GT samples of hypospadiac male rats（from DBP treated group）and normal rats（from control group）were collected.Furthermore,Western blot analysis was used to quantify expression of β-catenin,GSK-3β and NF-κB in genital tubercle （GT） of hypospadiac male rats.Results：The body weight and the anogenital distance（AGD） of fetal male rats significantly decreased in DBP treated group.Moreover,the expression of β-catenin was significantly decreased,and an increased expression of GSK-3β and NF-κB in GT was observed （P 0.05） in hypospadiac male rats.Conclusion：DBP could possibly affect the development of GT by regulating Wnt/β-catenin and NF-κB pathway in fetal male rats.

关 键 词：邻苯二甲酸二丁酯 尿道下裂 生殖结节 Wnt/β-连环蛋白信号通路 NF-ΚB 

分 类 号：R992[医药卫生—毒理学]