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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 To evaluate the reproductive toxicity and mechanism of dibutyl phthalate (DBP) in adolescent male rats. Methods Male Wistar rats (28 days old) were intragastrically administrated with DBP at doses of 1 000, 500 and 250 mg / (kg · d) for 8 weeks, respectively. Clinical symptoms were observed, body weight was recorded, blood Zn and hormone levels, fertility test, anatomy and histopathology were performed. Results The animals in the 1 000 mg / (kg · d) dose group experienced a significant decrease in body weight after 5 weeks (70% of the control group), and continued until the fifth week of the convalescence. Serum testosterone levels were reduced in the 1 000 mg / (kg · d) and 500 mg / (kg · d) dose groups for 8 weeks (80% -90% in the control group), and resumed after 4 weeks Normal; E2 levels of animals increased by 170% ~ 200% in the control group at 1000 mg / (kg · d) and 500 mg / (kg · d) .D) and 500 mg / (kg.d) dose group increased serum FSH levels (120% -150% of the control group) at 8 weeks; 1 000 mg / (kg.d) and 500 mg / kg.d), the sperm counts decreased after 8 weeks (12% -66% of the control group), and the mating success rate was 0 (0/8) in the 1 000 mg / (kg.d) , And the success rate of mating was 88% (7/8) in the group of 500 mg / (kg · d) for 8 weeks. The coefficient of testis in the group of 1 000 mg / (kg · d) significantly decreased compared with the control group, Histopathology showed that 1 000 mg / (kg.d) dose group of severe damage to the seminiferous epithelium, spermatogenic cells off, the damage of seminiferous tubules was 97.8%, with the difference between the control group were statistically significant significance. Conclusion DBP has obvious reproductive toxicity in male adolescent rats, and has the effect of interfering with reproductive endocrine hormone levels, lowering testosterone levels, estrogen and FSH levels, and inducing atrophy of testis, degeneration of germinal epithelium and loss of germ cells. . In our study, the lowest observed adverse effect level (LOAEL) of DBP in Wistar rats was 250 mg / (kg.d).