文章摘要
邻苯二甲酸二正丁酯(DBP)通过降低雄激素浓度促使自噬导致尿道下裂发生机制研究
Reduced androgen level induces autophagy leading hypospadias caused by Di-n-butyl phthalate (DBP)
投稿时间:2019-07-01  修订日期:2019-07-01
DOI:
中文关键词: 邻苯二甲酸二丁酯  尿道下裂  雄激素  自噬
英文关键词: Dibutyl phthalate  Hypospadias  Androgen  Autophagy
基金项目:国家自然科学基金(81771564),上海浦江人才计划(17PJD033)
作者单位E-mail
陈敏 上海交通大学附属第一人民医院 min_chen11@126.com 
潘磊 Department of Urology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
赵圣 Department of Urology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
朱依萍 Department of Urology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
周征 Department of Urology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
孙文兰 Department of Geriatrics ,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
蒋君涛 Department of urology ,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai  
董胜利 上海交通大学附属第一人民医院 dsl0596@163.com 
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中文摘要:
      目的:验证邻苯二甲酸二正丁酯(DBP)是通过降低血清雄激素水平导致自噬异常激活,探讨DBP致子代大鼠尿道下裂发生的具体机制。 方法:将孕鼠随机分为DBP染毒组与对照组,并于妊娠期14-18天分别灌胃给予DBP(750 mg/kg/天)及等量花生油。成功构建了子代新生大鼠尿道下裂模型。用免疫组织化学(IHC)染色观察生殖结节(GT)组织中自噬水平;用放射免疫分析方法测子鼠双氢睾酮(DHT)水平。在原代大鼠尿路上皮细胞(PUECs)用Western印迹检测PUECs中LC3I、LC3II及Beclin1表达水平。 结果:DBP染毒组尿道下裂发生率为42.3 %,对照组子代无尿道下裂。DBP染毒组子代GT组织中自噬表达增加。对照组中血清睾酮水平(n=10)较DBP染毒组(n=10)有明显差异(P<0.05)。体外研究表明对照组Beclin1及LC3蛋白较DHT缺乏组表达水平降低。 结论:孕期暴露于DBP可以诱发子代尿道下裂发生,这可能是由于DBP降低子鼠雄激素水平促使自噬发生导致的。
英文摘要:
      Objective: To verify that reducing levels of serum androgen can induce abnormal activation of autophagy by di-n-butyl phthalate (DBP) during maternal exposure and exploring the specific mechanism of DBP-induced hypospadias in offspring. Methods: Pregnant rats were randomly divided into the DBP-treated group and the control group, while DBP (750 mg/kg/day) and equivalent peanut oil were intragastrically administered on the 14-18 days during gestation. The hypothalamic model of the offspring of newborn rats was successfully constructed. The level of autophagy in the genital tubercle(GT) was observed by immunohistochemistry (IHC) staining. The level of dihydrotestosterone (DHT) in the rats were measured by radioimmunoassay. The expression levels of LC3I, LC3II and Beclin1 were detected by Western blot in primary urethral epithelial cells (PUECs). Results: The rate of hypospadias in the DBP-treated group was 42.3 %, while no hypospadias was observed in the control group. Autophagy expression was increased in GT tissues of DBP-treated groups. The levels of serum testosterone in the DBP group (n=10) were significantly different from those in the control group (n=10) (P<0.05). In vitro studies, we found that the Beclin1 and LC3 proteins in the DHT-deficient group were lower than those in the control group. Conclusions: Maternal Exposure to DBP can induce hypospadias, which may be due to DBP-induced autophagy by reducing serum androgen in offspring.
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