目的探讨邻苯二甲酸二(2-乙基已基)酯(DEHP)和氯氰菊酯(CYP)单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响。方法选择SPF级3周龄雄性SD大鼠24只,随机分为4组,分别为对照组(喂饲玉米油)、DEHP染毒组(500mg/kg)、CYP染毒组(80mg/kg);DEHP、CYP联合染毒组(DEHP500mg/kg+CYP80mg/kg),每组6只。采用经口灌胃方式染毒,每天1次,连续染毒30天。于末次染毒24小时后处死动物,测定大鼠体重、睾丸湿重,并计算睾丸系数;测定血清睾酮水平;制备睾丸病理组织切片,光镜观察其组织学改变,电镜观察生殖细胞超微结构;测定睾丸标志酶乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(ALP)和琥珀酸脱氢酶(SDH)的活性。结果与对照组相比,DEHP、CYP单独及联合染毒组睾丸下降时间和包皮分离时间明显延迟,肛门生殖器间距明显缩短(P〈0.05或0.01);DEHP单独染毒组睾丸重量及睾丸系数明显降低,血清睾酮水平显著下降(P〈0.05),睾丸匀浆中ALP、ACP和LDH活性明显增高,SDH活性显著下降(P〈0.01);DEHP、CYP单独及联合染毒组睾丸病理组织学、生殖细胞超微结构均可见明显异常。结论DEHP、CYP单独及联合柒毒对青春前期雄性大鼠均具有明显的生殖毒性作用,可引起生精细胞、支持细胞和间质细胞的变性、坏死及功能障碍,从而导致雄性生殖系统发育和功能的显著异常。其中,DEHP单独染毒呈现主效应,DEHP、CYP联合染毒对大鼠的生殖毒性未呈现明显交互影响。
Abstract:Objective To investigate the separate and combined toxic effects of di-2- ethylhexylphthalate (DEHP) and cypermethrin(CYP) on prepubertal male rats. Methods A total of 24 healthy 3-week-old SPF male Sprague-Dawley rats were randomly divided into four groups. They were control group(fed with corn oil) , DEHP group(500 mg/kg, dissolved in corn oil) , CYP group (80mg/kg, dissolved in corn oil) , combine group(DEHP 500mg/kg + CYP 80mg/kg, dissolved in corn oil), respectively. Each group consists of 6 rats. All the rats were exposed to DEHP or CYP by the means of gavage administration, once a day for 30 days. They were executed 24 hours after the last administration, and their weight, wet weight of the testis and testis coefficient was calculated. The histomorphological examination of the testis was conducted and the serum testosterone level was measured by Radioimmunoassay. The activities of LDH, ACP, ALP and SDH were assessed in testis homogenate. Results Compared with control group, the time of testicular descent and preputial separation was significantly delayed and the anogenital distance was significantly shorter in DEHP group, CYP group and combine group(P 〈0.05 or 0.01 ). In DEHP group, the wet weight of testis, testis coefficient and the serum level of testosterone were significantly decreased (P 〈 0.05 ). The activity of ALP, ACP and LDH in testis homogenate was significantly increased, but that of SDH was significantly decreased (P 〈 0.01 ). Histologic structure and uhrastructure of testis showed obvious abnormalities in DEHP group, CYP group and combine group. Conclusions DEHP and CYP had obviously separate and combined reproductive toxicity to prepubertal male rats. Both of them could cause the degeneration, necrosis and dysfunction of the seminiferous epithelium, sertoli cells and leydig cells and resulted in the abnormal development and function of the male reproductive system. Rats exposed to DEHP alone showed main toxic effect. There was no inter