邻苯二甲酸二丁酯对青春期雄性大鼠的生殖毒性研究  

Reproductive Toxicity of Di-n-butyl Phthalate in Puberty Male Rats

作　　者：常兵[1] 刘德瑜 梁玉香[1] 吴燕婉 

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [2]国家计划生育科学技术研究所

出　　处：《中国自然医学杂志》2007年第3期164-168,共5页Chinese Journal of Natural Medicine

基　　金：国家自然科学基金资助项目(No.30150003);科技部社会公益研究项目(No.2001DIB0059);教育部留学回国人员科研启动基金(2001)

摘　　要：目的评价邻苯二甲酸二丁酯（DBP）对青春期雄性大鼠生殖毒性和作用机制。方法用DBP剂量分别为1 000、500、250 mg/（kg.d）灌胃染毒雄性Wistar大鼠（28日龄）8周，并停止染毒后恢复8周。观察临床症状，记录动物体重，进行血Zn和激素测定、生殖能力检查和解剖及组织病理学等指标。结果1 000 mg/（kg.d）剂量组动物体重5周后出现显著下降（对照组的70%）、持续到停止染毒恢复期的第5周。1 000 mg/（kg.d）和500 mg/（kg.d）剂量组染毒8周时动物血清睾酮水平降低（对照组的80%-90%），停止染毒后第4周起恢复正常;1 000 mg/（kg.d）和500 mg/（kg.d）剂量组染毒8周时动物血清E2水平升高（对照组的170%-200%）;1 000 mg/（kg.d）和500 mg/（kg.d）剂量组染毒8周时动物血清FSH水平升高（对照组的120%-150%）;1 000 mg/（kg.d）和500 mg/（kg.d）剂量组染毒8周后精子计数减少（对照组的12%-66%），1 000 mg/（kg.d）剂量组染毒8周后交配成功率0（0/8），500 mg/（kg.d）剂量组染毒8周后交配成功率88%（7/8）;1 000 mg/（kg.d）剂量组睾丸系数与对照组比较明显减小，停止染毒后未见恢复;组织病理学发现1 000 mg/（kg.d）剂量组生精上皮严重损伤，生精细胞脱落，曲细精管的损伤度为97.8%，与对照组差异有统计学意义。结论DBP对雄性青春期大鼠具有明显的生殖毒性，具有干扰生殖内分泌激素水平的作用，使睾酮水平降低，雌激素和FSH水平升高，同时引起睾丸萎缩、生精上皮变性、生殖细胞脱落等损伤。本实验中DBP对Wistar大鼠的最低可观察毒性作用剂量水平（lowest observed adverse effect level，LOAEL）为250 mg/（kg.d）。Objective The purpose of this study was to evaluate the effects of male reproductive - endocrine system.challenged by di- n- butyl phthalate （DBP） in puberty male rats and to identify the mechanisms of the action. Method Male Wistar rats were used at the age of 4 weeks after birth and administrated with corn oil （control） and DBP [250, 500 or 1000 nag/ （kg·d）], respectively, for 8 weeks.After the exposure was stopped the animals were allowed to recover for 8 weeks and the animals were sacrificed then.The clinical symptoms, body weight, blood zinc and hormone concentrations, reproductive ability as well as morphology and histomorphology examinations of testicle of rat were taken. Resuls Total body weight gain were significantly reduced （70% of control group） at the doses of 1 000mg/ （kg·d）, but gradually recovered in 5 weeks after stopping exposure. Serum testosterone levels significantly reducedat the doses of 1000mg/ （kg·d） and500mg/ （kg·d） DBPtreatment groups （80%-90% of control group） after8 weeks＇ exposure but recovered after 4 weeks of stopping exposure. Serum estradiol levels showed significant increase at the doses of 1 000 mg/ （kg·d）and 500 mg/ （kg·d） DBP treatment groups （170% - 200% of control group） after 8 weeks＇ exposure. Serum FSH levels showed significant increase at the dose of 1 000 rag/ （kg·d） and 500 mg/ （kg·d） DBP treatment groups （ 120% - 150% of cantrol group） after 8 weeks＇ exposure.The sperm counting significant reduced at the doses of 1 000 mg/（kg·d）and 500 mg/（kg·＇d） DBP treatment groups （12% - 66% of control group） after 8 weeks＇ exposure.The successful mating rate was 0 （0/8） and 88% （7/ 8） at the dose of 1 000 mg/ （kg·d） and 500 mg/ （kg·d） DBP treatment groups, respectively, after 8 weeks＇ exposure.The ratio of testicle/body was significantly reduced at the dose of 1 000 mg/ （kg·d） DBP treatment groups than that of control, and no recovery was observed after stopping exposu

关 键 词：邻苯二甲酸二丁酯 生殖毒性 睾丸损伤 大鼠 

分 类 号：R994.6[医药卫生—毒理学]