两种邻苯二甲酸酯类物质的抗雄激素作用研究

Study of anti-androgenic effect of two of phthalate esters

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、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3.0 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 000mg/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。

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 castrated SD rats were randomly divided into 16 groups,DEHP（35,70,150,250,500,1 000 mg/kg BW）and DBP（70,150,250,500,750,1 000 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,levatoranibulbocavernosus muscles and Cowper＇s glands were significantly decreased in the group of 250,500 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 500,750 and 1 000 mg/kg BW DBP（P〈0.05）.Benchmark does of DEHP and DBP was 150.38 and276.78 mg/kg BW.Conclusion DEHP and DBP had anti-androgenic effects in vivo and weight of levatoranibulbocavernosus muscles and Cowper＇s glands are sensitive indexes.