【摘要】：目的:鄰苯二甲酸二丁酯(DBP)孕晚期染毒誘導(dǎo)雄性SD大鼠子鼠發(fā)生尿道下裂畸形,并進一步探討DBP致雄性子鼠發(fā)生尿道下裂的分子作用機制。方法:孕鼠20只,懷孕14~18 d,隨機分為對照組和DBP染毒組,每天分別予大豆油及DBP 750 mg/kg灌胃。出生后(PND)1 d,統(tǒng)計雄性子鼠中尿道下裂的發(fā)生率,觀察尿道下裂雄性子鼠生殖結(jié)節(jié)的病理學(xué)改變。放射免疫法檢測血清雄激素水平,實時熒光定量PCR和Western印跡檢測生殖結(jié)節(jié)中雄激素受體(AR)、音猬因子(Shh)、骨形態(tài)發(fā)生蛋白4(Bmp4)和成纖維細胞成長因子8(Fgf8)的mRNA和蛋白表達水平。結(jié)果:對照組中無尿道下裂發(fā)生,DBP染毒組中雄性子鼠尿道下裂發(fā)生率為43.6%,病理學(xué)檢查發(fā)現(xiàn)生殖結(jié)節(jié)典型的尿道下裂畸形。尿道下裂雄性子鼠的血清雄激素水平[(0.49±0.05)ng/ml]較對照組[(1.12±0.05)ng/ml]明顯降低(P0.05),生殖結(jié)節(jié)中AR、Shh、Bmp4和Fgf8基因的mRNA水平(0.50±0.05、0.65±0.07、0.42±0.05、0.46±0.04)較對照組(1.00±0.12、1.00±0.15、1.00±0.13、1.00±0.12)明顯降低(P0.05),蛋白水平(0.34±0.05、0.51±0.07、0.43±0.05、0.57±0.04)較對照組(1.00±0.09、1.00±0.12、1.00±0.11、1.00±0.13)明顯降低(P0.05)。結(jié)論:孕晚期DBP染毒可以導(dǎo)致雄性子鼠發(fā)生尿道下裂畸形。DBP通過降低雄性子鼠血清雄激素水平和生殖結(jié)節(jié)中AR、Shh、Bmp4、Fgf8基因的表達,影響生殖結(jié)節(jié)的正常發(fā)育,是DBP導(dǎo)致尿道下裂畸形發(fā)生的可能機制。
[Abstract]:Aim: to induce hypospadias in male SD rats induced by dibutyl phthalate (DBP) in late pregnancy and to explore the molecular mechanism of hypospadias induced by DBP. Methods: twenty pregnant rats were randomly divided into two groups: control group and DBP group. Soybean oil and DBP 750 mg/kg were administered daily. The incidence of hypospadias in male hypospadias and the pathological changes of reproductive nodules in male hypospadias were observed 1 day after (PND). Serum androgen levels were detected by radioimmunoassay and mRNA and protein expressions of androgen receptor (AR), sound hedgehog factor (Shh), (Bmp4) and fibroblast growth factor 8 (Fgf8) in reproductive nodules were detected by real-time fluorescence quantitative PCR and Western blotting. Results: there was no hypospadias in the control group. The incidence of hypospadias was 43.6 in the male hypospadias treated with DBP. The typical hypospadias deformity of reproductive nodules was found by pathological examination. 灝塊亾涓嬭闆勬，

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