氟他胺诱导尿道下裂大鼠模型的建立及其作用机制  

Establishment of Hypospadias Rat Model Induced by Flutamide and the Mechanism

作　　者：李岩[1] 张浩[2] 吴德生[2] 

机构地区：[1]遵义医学院预防医学教研室,563003 [2]四川大学华西公共卫生学院环境卫生教研室,610041

出　　处：《贵州医药》2007年第3期195-198,共4页Guizhou Medical Journal

基　　金：国家自然科学基金重点课题(30030120);纽约中华医学会(CMB)资助

摘　　要：目的用氟他胺诱导建立尿道下裂大鼠模型并在分子水平研究其导致尿道下裂的作用机制。方法将孕鼠在第12～17天用氟他胺(6 054．6μg/kg)连续每天皮下注射染毒建立子代雄鼠尿道下裂模型,另在第20天行破宫产取子代雄鼠的睾丸组织,用逆转录聚合酶链反应(RT-PCR)的方法检测睾酮合成过程中细胞色素P450胆固醇侧链裂解酶(P450scc)、3β羟基类固醇脱氢酶(3β- HSD)和细胞色素P450 17α-羟化酶(P450c17)等关键酶基因的活性表达水平。结果氟他胺诱导的尿道下裂胚胎鼠睾丸组织中P450scc、3-β-HSD和P450c17等的基因活性表达水平较正常对照组均有不同程度的下降。结论氟他胺通过在性发育期干扰子代雄鼠睾丸组织中睾酮的生物合成途径,降低了睾酮水平,导致子代雄性大鼠尿道下裂的发生。Objective To establish hypospadias rat model induced by flutamide （Flu） and to study the mechanism. Methods Pregnant Sprague-Dawley rats were injected subcutaneously with Flu at 6 054.6μg/kg every day as Flu-exposed group on gestation days （GD） 12-17 to estabish hypospadias rat model and testicular RNA isolated from GD 20 fetuses testis was used for real-time RT-PCR for the following genes： P450 side-chain cleavage enzyme （P450scc）, 3βhydroxysteroid dehydrogenase （3β-HSD）, cytochrome P450 17α-hydroxylase （P450c17） etc. Results The activity of P450scc, 3β-HSD and P450c17 etc in the Flu -exposed fetal testes were decreased as compared with control group. Condusion Flu altered gene expression of the five enzymes except AR in the testicular testosterone （T） biosynthetic pathway and decreased T production, resulting in the occurrence of hypospadias in SD rat.

关 键 词：氟他胺 尿道下裂 逆转录-聚合酶链反应 

分 类 号：R695[医药卫生—泌尿科学]