氟他胺对尿道下裂相关凋亡基因表达影响

Expression of correlative apoptosis gene of hypospadias induced by flutamide

目的探讨氟他胺(Flu)诱导尿道下裂形成过程中相关凋亡基因的表达水平,研究其导致尿道下裂的作用机制。方法将孕鼠在第12～17d用氟他胺(6.0546 mg/kg)连续每天皮下注射染毒,在第20 d行破宫产取子代雄鼠的尿道生殖结节和睾丸,用免疫组化和基因芯片技术检测氟他胺致尿道下裂形成相关凋亡基因的表达水平。结果Ful染毒组胚胎20 d SD大鼠生殖结节、间充质细胞和尿道细胞中表皮生长因子(EGF),表皮生长因子受体(EGFR)的表达减弱;半胱氨酸天冬氨酸蛋白酶3(caspase-3)等相关凋亡基因的表达增强。图像灰度值两样本均数的比较显示,对照组灰度值与染毒组灰度值差异均有统计学意义(P<0.05)。结论氟他胺通过在性发育期干扰子代雄鼠尿道生殖结节和睾丸组织中相关凋亡基因的表达水平,导致子代雄性大鼠尿道下裂的发生。

Objective To explore the expression level of correlative apoptosis gene of hypospadias induced by flutamide （Flu） and study the mechanism. Methods Pregnant SD rats were injected subcutaneously with Flu at 6.0546mg/kg every day on gestation days（GD）12-17 and genital tubercle and testes from GD20 fetuses were extrated to detect the expression level of correlative apoptosis gene by the means of immunohistochemistry and DNA chip. Results The expression of the EGF, EGFR of the SD rats decreased in genital tubercle, mesenchymal cell and urethral cells, while the expression of caspase - 3 correlative apoptosis gene increased. The gray scales of the control group and experimental group were different. All of the differences between the two groups were significant in statistics（ P 〈 0.05）. Conclusion Flu can alter the expression level of correlative apoptosis gene in the genital tubercle and testis, inducing the hypospadias in F1 male rat.