【作者】 马隆；

【导师】 张炜；

【作者基本信息】 南京医科大学 ， 泌尿外科， 2007， 硕士

【摘要】 目的：研究邻苯二甲酸二丁酯(DBP)孕晚期染毒诱导雄性大鼠发生尿道下裂的分子作用机制。方法：SD雌性大鼠怀孕(GD)第14-18天，称重后每天分别灌胃予大豆油，DBP 500或800mg／kg／day，雄性仔鼠出生后(PND)第1天，鉴别出DBP染毒组中发生尿道下裂的雄性仔鼠，分组为雄性仔鼠对照组(A组)，500mg／kg／day(H)(B组)和800mg／kg／day(H)(C组)。用实时定量逆转录聚合酶链反应(Real-time quantitative RT-PCR)方法检测阴茎组织中sonic hedgehog(Shh)，骨形态发生蛋白4(Bmp4)和雄激素受体(Ar)mRNA表达水平。用Western blotting测量阴茎组织中Ar蛋白表达水平。用放射免疫分析(RIA)方法测定血清睾酮(T)水平。结果：B组在mRNA(shh，Ar)表达水平和血清T水平较对照组有明显的降低(P＜0.05)，C组在mRNA(Shh，Bmp4，Ar)和蛋白(Ar)表达水平以及血清T水平都较对照组有明显的降低(P＜0.05)。结论：DBP通过对生殖结节(GT)生长发育早期的Shh信号系统，以及晚期的雄激素信号系统发生作用而影响GT的生长发育，诱导尿道下裂的发生。更多还原

【Abstract】 Objective: The objective of this study was to investigate molecularmechanisms of hypospadias in male rats exposed to di-n-butyl phthalate(DBP) during late gestation.Methods: Timed pregnant Sprague-Dawley (SD) rats were givenDBP by gastric intubation at a dose of 0, 500 or 800 mg/kg/day fromgestation day (GD) 14 to 18 after maternal body weight was recordeddaily. On postnatal day (PND) 1, male offspring were allocated to threegroups: control male offspring (group A), 500 mg/kg/day (H) (group B)and 800 mg/kg/day (H) (group C) after identifying control male offspringnot exposed to DBP and hypospadiac male offspring exposed to DBP.Real-time quantitative RT-PCR and Western blotting were used toquantify mRNA of sonic hedgehog (Shh), bone morphogenetic protein 4(Bmp4) and androgen receptor (Ar) and protein of Ar expression in ratpenises of above three groups on PND 1. Serum testosterone (T)concentration of male offspring in above three groups on PND 1 wasdetermined by using T radioimmunoassay (RIA) kit. Results: mRNA (Shh, Ar) expression in rat penises and serum Tlevel in group B were significantly decreased compared with those incontrol group (P＜0.05). mRNA (Shh, Bmp4, Ar), protein (Ar) expressionin rat penises and serum T level in group C were significantly decreasedcompared with those in control group (P＜0.05).Conclusions: DBP affects the development of the genital tubercle(GT) by regulating Shh signaling in early development of GT andandrogen signaling in late development of GT, inducing the occurrence ofhypospadias in male rats.更多还原