DEHP对大鼠睾丸氧化应激和血清睾酮水平影响

目的 探讨邻苯二甲酸二乙基己酯（DEHP）对青春期雄性大鼠睾丸及性激素的影响及潜在机制。方法 18日龄SD大鼠24只，按体重随机分为4组（对照组、低、中、高剂量DEHP组），每组6只。DEHP染毒剂量分别为250、500和750 mg/kg，经口连续染毒30 d；颈部脱臼处死，收集血清，分离睾丸组织；测定血清睾酮、黄体生成素（LH）和卵泡刺激素（FSH）等性激素水平及睾丸组织中谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛和5α-还原酶（5α-R）活性。结果 DEHP处理组，大鼠睾丸和附睾脏器系数降低，睾丸曲精小管管腔缩小，结构坍塌，部分细胞膜破裂，细胞排列紊乱；与对照组比较，高剂量DEHP组大鼠血清睾酮和LH水平[分别为（115.04±14.21） pg/mL、（23.42±3.12） mIU/mL]降低，中、高剂量DEHP组大鼠血清FSH水平[分别为（5.49±0.42）、（4.63±0.51） IU/L]下降，差异有统计学意义（P<0.05）；与对照组比较，高剂量DEHP组大鼠睾丸组织中GSH-Px和SOD活力[分别为（728.3±95.3）、（835.8±151.2） U/mg pro]降低，而中、高剂量DEHP组大鼠睾丸组织中丙二醛含量[分别为（79.6±13.9）、（90.6±4.0） nmol/mg pro]和5α-R2活性[分别为（415.9±112.7）、（415.9±147.8） IU/mg pro]升高，差异有统计学意义（P<0.05）。结论 DEHP暴露后，大鼠睾丸发生氧化应激，并通过诱导5α-R2活性降低血清睾酮水平。

DEHP-induced testicular oxidative stress and down-regulated serum testosterone in rats

Objective To explore effects and potential mechanisms of di-(2-ethylhexyl) phthalate (DEHP) on testes and sex hormones in pubertal male rats.Methods Twenty-four 18-day-old male Sprague-Dawley rats were randomly divided into 4 groups (control,low-,moderate-,and high-dose groups,6 rats in each group) by weight.The rats of dose groups were gavaged with DEHP at doses of 250,500,750 mg/kg/d for 30 days.All rats were sacrificed by decapitation at the end of the treatments.Serum samples were collected and reproductive organs were removed and weighted.Serum testosterone (T),luteinizing hormone (LH),follicle-stimulating hormone (FSH),gonadotropin releasing hormone (GnRH),and 5α-dihydrotestosterone (5α-DHT) levels and testicular glutathione peroxidase (GSH-Px),superoxide dismutase (SOD),malondialdehyde (MDA),and 5α-reductase 2 (5α-R2) levels were measured.Results In the rats exposed to DEHP,the testis index and epididymis index were decreased.Tubular lumina shrinking,structure collapse,breaks of cell membranes,and disordered cell arrangement of seminiferous tubules were observed in the DEHP-treated rats.Levels of T (115.04±14.21 pg/mL) and LH (23.42±3.12 mIU/mL) in the high-dose group were significantly declined compared with those of the control.In moderate-and high-dose groups,FSH levels (5.49±0.42 and 4.63±0.51 IU/L) were significantly lower (P<0.05) than those of the control.Moreover,significantly decreased GSH-Px (728.3±95.3 U/mg pro) and SOD (835.8±151.2 U/mg pro) activities in rat testis were also detected in the high-dose group;on the contrary,MDA level (79.6±13.9 and 90.6±4.0 nmol/mg pro) and 5α-R2 activity (415.9±112.7 and 415.9±147.8 IU/mg pro) in the moderate-and high-dose groups were significantly higher than those of the control (P<0.05 for all).Conclusion After exposure to DEHP,oxidative stress occurred in the testis and serum testosterone level was down-regulated via inducing decreased activity of 5α-reductase 2.