摘要
目的用邻苯二甲酸二（2-乙基）己酯（DEHP）诱导建立先天性尿道下裂小鼠模型．研究DEHP对胎鼠阴茎内转化生长闲子β1（TGF-β1）表达的影响。探讨尿道下裂发生机制。方法C57BL／6孕鼠随机分为4组：玉米油对照组、DEHP低、中、高剂量组（100、200、500mg·kg^-1·d^-1）。各组分别于母鼠孕期12d至17d（GD12～17）持续经口灌注给药。测量GD19雄性胎鼠体重、肛门至尿道口距离（AGD），通过尿道管型（UC）检测尿道解剖组织结构，比较尿道发育情况。应用免疫印迹（Western blot）检测胎鼠阴茎内TGF-β1蛋白量的表达水平。结果DEHP成功诱导出尿道下裂小鼠动物模型，中、高剂量组A（；D及前尿道较对照组明显缩短（P〈0．001）。实验组阴茎内TGF—β1蛋白表达水平随DEHP剂量增加而逐渐上升。结论DEHP成功诱导建立先天性尿道下裂小鼠模型，胎鼠阴茎内TGF-β1蛋白异常表达可能是尿道下裂的发生机制之一。
Objective To induce hypospadias in mice with di（2-ethylhexyl）phthalate （DEHP）, and investigate the expression of TGF-β1 in fetal mice genital tubercles. Methods Pregnant C57BL/6 mice were randomly divided into 4 groups： control and DEHP （101）, 200, 500 mg·kg^-1 ·d ^-1 ） groups. Mice were gavaged from gestation day 12 to 17 （GD12-17）. Fetal mice were harvested at GD19. We established urethral casts （UC） to compare urethral development, following the analyzed body weight and anogenital distance （AGD）. The level of TGF -β1 protein was investigated by western blot. Results Hypospadias was induced in fetal male mice The AGD and anterior urethra length in DEHP 200 mg· kg^- 1 · d ^-1 and 500 mg·kg^-1 ·d ^-1 groups were significantly shorter than those of control group （P〈0. 001）. The levels of TGF-β1 protein were ut〉regulated in experimental groups and positively related with the dose of DE- HP. Conclusions Murine model of hypospadias has been established successfully by treatment with DEHP, and up-regulated TGF-β1 protein may be one of the pathogenesis of hypospadias.
出处
《中华小儿外科杂志》
CSCD
北大核心
2008年第9期565-568,共4页
Chinese Journal of Pediatric Surgery
关键词
转化生长因子Β
尿道下裂
小鼠
Transforming growth factor beta
Hypospadias
Mice
