环磷酰胺对大鼠生育力与早期胚胎发育毒性的比较研究

发布时间：2018-02-27 16:00

本文关键词： 环磷酰胺生殖毒性发育毒性阳性对照　出处：《毒理学杂志》2015年05期 　论文类型：期刊论文

【摘要】：目的比较不同剂量与给药途径对环磷酰胺致大鼠生育力与早期胚胎发育毒性。方法雌雄SD大鼠,随机分为4组:环磷酰胺A组、B组(分别皮下注射40和20 mg/kg),环磷酰胺C组(腹腔注射20 mg/kg)和阴性对照组(空白)。雄鼠合笼前给药5次(每周1次),雌鼠合笼前给药3次(每周1次),交配成功雌鼠于妊娠期第4天(GD4)再给药1次。雄鼠于交配成功后解剖,雌鼠于GD15解剖,考察精子浓度和活动度,生殖器官脏器重量和系数,胚胎发育指标,性激素水平等。结果与阴性对照组比较,环磷酰胺A组雌雄大鼠体重,摄食量,子宫和卵巢脏器重量及系数,睾丸和附睾脏器重量,精子数量和活力各项指标,子宫连胎重、着床、活胎、吸收胎、着床前/后丢失数(率)等胚胎发育指标,雄鼠的睾酮和孕鼠的雌二醇水平等均显示明显毒性改变;而B组和C组仅部分指标出现毒性改变,且毒性程度弱于A组。结论在本试验条件下,皮下注射40 mg/kg环磷酰胺可以得到较全面的明显的亲代雌雄大鼠生殖毒性和早期胚胎发育毒性阳性结果,可以作为阳性对照模型。
[Abstract]:Objective to compare the effects of different doses and ways of administration on the fertility and early embryonic development of rats induced by cyclophosphamide. Methods male and female Sprague-Dawley rats were used. They were randomly divided into 4 groups: cyclophosphamide A group (40 mg / kg / kg), cyclophosphamide C group (20 mg / kg intraperitoneal injection) and negative control group (5 times a week) (once a week). Three times (once a week, one time per week, female mice were given GD4 on the 4th day of gestation), and the male mice were dissected after mating. Female rats were dissected at GD15 to investigate sperm concentration and activity, organ weight and coefficient of reproductive organs, embryonic development index, sex hormone level, etc. Results compared with negative control group, cyclophosphamide A group had male and female rats' body weight and food intake. Weight and coefficient of uterus and ovary organs, weight of testis and epididymis organs, sperm count and motility, fetal weight of uterus, implantation, live fetus, absorption fetus, number of lost before and after implantation, and so on. The levels of testosterone and estradiol in male rats and pregnant rats showed obvious toxic changes, but only some of the indexes in group B and C showed toxic changes, and the degree of toxicity was weaker than that in group A. Conclusion under the present condition, the toxicity of testosterone in group B and group C is lower than that in group A. Subcutaneous injection of 40 mg/kg cyclophosphamide could obtain more comprehensive positive results of reproductive toxicity and early embryonic development toxicity of male and female rats, and could be used as a positive control model.
【作者单位】：浙江省医学科学院安全性评价研究中心;
【基金】：国家“十二五”科技重大专项(2011ZX09301-003) 浙江省科技计划项目(2014F30018) 浙江省医药卫生科技计划项目(2014KYA046)
【分类号】：R114

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