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目的:邻苯二甲酸二丁酯(dibutyl phthalate,DBP)孕晚期暴露诱导子代Spraque-Dawley大鼠发生尿道下裂,探讨Akt信号通路及其下游关键蛋白核转录因子κB(nuclear factor-κ-gene binding,NF-κB)在胎鼠生殖结节中的差异表达,研究该通路在DBP致大鼠生殖系统发育异常过程中的作用机制。方法:孕SD大鼠20只,随机分为染毒组和对照组,在妊娠时间(gestation day,GD)14～18 d,每天通过灌胃分别给予DBP 800 mg/kg和大豆油,在GD19时提取染毒组发生尿道下裂胎鼠与对照组胎鼠的生殖结节组织,用Western blot检测磷酸化Akt(p-Akt)、Akt和NF-κB的表达情况,同时用免疫组化分析p-Akt的表达情况。结果:尿道下裂组与对照组中p-Akt、Akt和NF-κB相对表达量的比值分别为3.057±0.026、2.624±0.073和3.524±0.035(n=10,P<0.05),且尿道下裂组中p-Akt蛋白相对量在总蛋白中所占的比例较对照组高。p-Akt定位于生殖结节上皮细胞,尿道下裂组p-Akt染色明显强于对照组。结论:DBP干预大鼠生殖结节中Akt信号通路及其下游NF-κB的正常表达,进而影响了上皮细胞增殖、凋亡及尿生殖褶的融合,这可能是尿道下裂发生的机制之一。
AIM: To investigate the relationship between Akt signaling pathway and its downstream key nuclear factor-κB (NF-κB) gene in the second generation of Spraque-Dawley rats exposed to dibutyl phthalate (DBP) gene binding, NF-κB) in fetal rat reproductive nodules, and to explore the mechanism of this pathway in the process of DBP-induced reproductive development in rats. Methods: Twenty pregnant SD rats were randomly divided into treatment group and control group. Gestational time (gestation day, GD) was 14-18 days. DBP 800 mg / kg and soybean oil were given daily by gavage. The genital nodules were extracted from fetus of fetus with urethra and control group, and the expression of phosphorylated Akt (p-Akt), Akt and NF-κB were detected by Western blot. Immunohistochemistry p-Akt expression. Results: The ratio of p-Akt, Akt and NF-κB in hypospadias group and control group were 3.057 ± 0.026, 2.624 ± 0.073 and 3.524 ± 0.035 respectively (n = 10, P <0.05) Cleft group in the relative amount of p-Akt protein in the proportion of total protein than the control group. p-Akt located in the reproductive nodules epithelial cells, hypospadias p-Akt staining was significantly stronger than the control group. Conclusions: DBP interfered with the Akt signaling pathway and its downstream normal expression of NF-κB in the rat reproductive nodules, which in turn affected the proliferation of epithelial cells, apoptosis and the fusion of urogenital folds, which may be one of the mechanisms of hypospadias .