两种邻苯二甲酸酯物质的抗雄激素作用研究.doc

两种邻苯二甲酸酯物质的抗雄激素作用研究 摘要：目的 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大鼠为试验动物，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、1000 mg/kg.bw，DBP剂量分别为70、150、250、500、750、1000 mg/kg.bw；阴性对照组和阳性对照组分别灌胃给予玉米油和3.0mg/kg.bw氟他胺，连续10天。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、1000 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（P0.05），500、750、1000 mg/kg.bw DBP剂量组肛提肌-海绵体肌、尿道球腺低于对照组（P0.05），各组间血清激素水平无显著差异；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 DEHP、DBP经口摄入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。 邻苯二甲酸二（2-乙基）己酯邻苯二甲酸二丁酯Hershberger试验；抗雄激素；内分泌干扰；基准剂量； Study for anti-androgenic effect of two of Phthalate esters Abstract：Objective 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 SD rats were randomly divided into 16 groups, DEHP( 35, 70, 150, 250, 500, 1000 mg/kg.bw) and DBP ( 70, 150, 250, 500, 750, 1000 mg/kg.bw ) were given by oral gavage, respectively. Meanwhile, coin 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, 0.2mg/kg.bw Testosterone Propionate was given to every groups 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, 500 and 1000 mg/kg.bw DEHP (P0.05) , and weight of levatorani-bulbocavernosus muscles and Cowper’s glands were signific