Smad7,Smad3和Smad2在DEHP诱导的尿道下裂大鼠阴茎中的表达  

Exprssion of Smad7,Smad3 and Smad2 in the hypospadiac penis of fetal rats induced by DEHP

作　　者：李明勇[1] 王星 石秦林 魏光辉[2] 曹友汉[1] 邓湘[1] 许韩峰[1] 李清[1] 

机构地区：[1]南华大学附属第一医院泌尿外科科室,湖南省衡阳市421001 [2]重庆医科大学附属儿童医院泌尿外科科室,重庆市400014

出　　处：《临床小儿外科杂志》2018年第2期136-140,共5页Journal of Clinical Pediatric Surgery

基　　金：国家自然科学基金青年基金项目(81401190)

摘　　要：目的研究Smads(7,3和2)在邻苯二甲酸二(2-乙基)己酯[di-(2-ethylhexyl)phthalate,(DEHP)]诱导的尿道下裂大鼠阴茎组织中的表达变化,探讨尿道下裂发生机制。方法将SD孕鼠随机分为2组:实验组(将DEHP溶于1.5 mL大豆油中灌胃大鼠)和对照组(以1.5 mL大豆油灌胃大鼠),每组20只,自孕12 d(gestation day,GD12)至19 d(GD19)连续每天定时给药1次。至GD20行剖宫产取出雄性胎鼠,切取阴茎组织,采用实时定量PCR和免疫组化法分别检测胎鼠阴茎中Smad7,Smad3和Smad2三者mRNA和蛋白质表达水平。结果经qP CR检测分析后发现,Samd7,Smad3和Smad2三者mRNA在正常对照组相对于内参GAPDH的表达分别是1.00,0.84和1.14,在DEHP暴露组其相对表达分别是1.87,1.36和1.49,且三者在实验组的表达与正常对照组比较,均升高(P值分别为<0.001,0.041和0.021);观察实验组Smad7和p-Smad2/3蛋白表达水平亦有增加趋势。结论DEHP诱导的先天性尿道下裂可能与胎鼠阴茎组织中Smads(7,3和2)的过度表达有关。Objective To investigate the expression of Smads( 7,3 and 2) in the hypospadias penis of fetal rats induced by maternal exposure to di-( 2-ethylhexyl) phthalate( DEHP),in order to explore the etiology of hypospadias. Methods Pregnant rats were randomly divided into experiment group and control group,20 rats for each group. Each rat in the experiment group was treated with DEHP dissolved in 1. 5 ml soybean oil by savaging,while control group were treated with 1. 5 ml soybean oil,once a day from the 12 th gestation days( GD12) to GD19. Fetal rats were obtained on the GD20 by caesarean section,and were investigated for the mRNA and protein expression levels of Smad7,Smad3 and Smad2 by using real-time quantitative PCR and immunohistochemistry assay respectively. Results The expression of Smad7,Smad3 and Smad2 mRNA in hypospadias rats foreskin tissue increased 97. 0%,22. 8% and 59. 9% times compared with normal control groups,respectively,and the differences were significant( all P < 0. 05). Moreover,the protein levels of Smad7 and phosphorylated Smad 2/3 in foreskin from children with hypospadias showed an incremental trend. Conclusion Our results preliminary indicate that Smads( 7,3 and 2) overexpression might be associated with the DEHP-induced congenital hypospadias.

关 键 词：尿道下裂 二乙基己基邻苯二甲酸 Smad7蛋白质 Smad3蛋白质 Smad2蛋白质 大鼠 

分 类 号：R726.9[医药卫生—儿科]