两种邻苯二甲酸酯类物质的抗雄激素作用研究
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(1.潍坊医学院公共卫生学院,山东 潍坊 261053;2.国家食品安全风险评估中心 卫生部食品安全 风险评估重点实验室,北京 100021;3.中国疾病预防控制中心营养与健康所,北京 100050)

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燕高峰 男 硕士生 研究方向为内分泌干扰物 E-mail:haidementu@163.com通信作者:┣┣(中)通信作者┫┫刘兆平 男 研究员 研究方向为食品毒理学和化学物风险评估 E-mail:liuzhaoping@cfsa.net.cn

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国家自然科学基金项目(81273081)


Study of anti-androgenic effect of two of phthalate esters
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(School of Public Health, Weifang Medical University, Shandong Weifang 261053, China)

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    摘要:

    探讨邻苯二甲酸二(2-乙基)己酯(DEHP)和邻苯二甲酸二丁酯(DBP)的抗雄激素作用。方法 参照OECD Hershberger试验指南进行,以6周龄雄性去势SD大鼠为实验动物,随机分为16组(7只/组),分别以DEHP和DBP为受试物,DEHP剂量分别为35、70、150、250、500、1 000 mg/kg BW,DBP剂量分别为70、150、250、500、750、1 000 mg/kg BW;阴性对照组和阳性对照组分别灌胃给予玉米油和3.0 mg/kg BW氟他胺,连续10 d。灌胃前各组均皮下注射丙酸睾酮。试验结束后测定阴茎头、腹侧前列腺、精囊、肛提肌-海绵体肌、尿道球腺重量和血清中睾酮、黄体生成素水平。利用基准剂量分析软件分析雄激素依赖器官重量的剂量-反应关系。结果 250、500、1 000 mg/kg BW DEHP剂量组腹侧前列腺、肛提肌-海绵体肌、尿道球腺重量低于对照组,差异有统计学意义(P<0.05);500、750、1 000 mg/kg BW DBP剂量组肛提肌-海绵体肌、尿道球腺低于对照组,差异有统计学意义(P<0.05),各组间血清激素水平差异无统计学意义(P>0.05);基准剂量分析发现,DEHP和DBP对肛提肌-海绵体肌、尿道球腺重量影响具有剂量-反应关系,两种物质抗雄激素作用的基准剂量下限分别为150.38和276.78 mg/kg BW。结论 经口摄入DEHP、DBP均会产生抗雄激素作用,肛提肌-海绵体肌、尿道球腺重量变化是较敏感指标。

    Abstract:

    Study the anti-androgenic effect of diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP).Methods According to Hershberger bioassay form OECD guideline, 6 weeks old male castrated SD rats were randomly divided into 16 groups, DEHP (35,0, 150,0, 500,1 000 mg/kg BW) and DBP (70,0, 250,0, 750,1 000 mg/kg BW ) were given by oral gavage, respectively. Meanwhile, corn oil was given by oral gavage as a negative control, and 3.0 mg/kg BW flutamide was given by oral gavage as a positive control for 10 consecutive days. In addition, 0.2 mg/kg BW testosterone propionate was given to each group by subcutaneously inject before gavage. In the end of test, animals were anesthetized, weight of glans penis, ventral prostate, seminal vesicles, levatorani-bulbocavernosus muscles, Cowper's glands were measured, testosterone and luteinizing hormone levels were measured. The dose-response were analyzed by benchmark does software. Results In comparison with negative control, weight of ventral prostate, levatorani-bulbocavernosus muscles and Cowper's glands were significantly decreased in the group of 250,0 and 1 000 mg/kg BW DEHP (P<0.05) , and weight of levatorani-bulbocavernosus muscles and Cowper's glands were significantly decreased in the group of 500,0 and 1 000 mg/kg BW DBP (P<0.05). Benchmark does of DEHP and DBP was 150.38 and 276.78 mg/kg BW.Conclusion DEHP and DBP had anti-androgenic effects in vivo and weight of levatorani-bulbocavernosus muscles and Cowper's glands are sensitive indexes.

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燕高峰,毛伟峰,贾旭东,张文众,李志华,初传传,陈晨,刘兆平.两种邻苯二甲酸酯类物质的抗雄激素作用研究[J].中国食品卫生杂志,2016,28(2):149-154.

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  • 收稿日期:2016-02-29
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  • 在线发布日期: 2016-04-20
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