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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 To investigate the anti-androgen action of di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP). METHODS: According to OECD Hershberger’s test guidelines, 6-week-old male SD rats were randomly divided into 16 groups (7 / group), with DEHP and DBP as the test substance respectively. The DEHP doses were 35, 70,150,250,500,1 000 mg / kg BW and DBP doses were 70,150,250,500,750,1000 mg / kg BW respectively. The negative control group and the positive control group were orally administered with corn oil and 3.0 mg / kg BW flutamide for 10 days. Each group was subcutaneously injected testosterone propionate before gavage. After the test, the penis head, ventral prostate, seminal vesicle, levator ani - cavernous muscle, urethral bulb weight and serum testosterone and luteinizing hormone were measured. Dose-response relationships for androgen-dependent organ weights were analyzed using benchmarking software. Results The weight of ventral prostate, levator ani muscle - cavernous muscle and urethral bulb in 250, 500 and 1000 mg / kg BW DEHP groups were lower than those in control group (P <0.05) 1 000 mg / kg BW DBP dose group levator ani - cavernous muscle, urethral bulb gland less than the control group, the difference was statistically significant (P <0.05), serum hormone levels between the groups showed no significant difference (P> 0.05 ); Baseline dose analysis found that DEHP and DBP had a dose-response relationship with the weight of the levator ani muscle-cavernous muscle and urethral gland. The lower limit of the baseline anti-androgens effect of the two substances were 150.38 and 276.78 mg / kg BW, respectively . Conclusion DBP can produce anti-androgen effect after oral ingestion of DEHP, and the weight change of levator ani muscle and cavernous muscle and urethral bulb is a sensitive index.