摘要
目的:研究新型雷公藤甲素衍生物MC004对雄性大鼠生育能力的影响。方法:雄性Wistar大鼠48只,随机分为4组。隔日尾静脉注射,分别给予0,0.25,0.50,0.75mg·kg-1的MC004,共28d。观察临床症状,记录动物体重,进行生育力检查并观察孕鼠各项妊娠指标变化。结果:与对照组相比,0.25mg·kg-1剂量组大鼠各项指标均未见明显变化;0.75mg·kg-1组大鼠生育率明显降低(P<0.01);与0.75mg·kg-1剂量组雄性大鼠交配的雌性大鼠子宫重,胎盘重,卵巢重,平均着床数,活胎窝数,总活胎数,窝均活胎数,活胎率均明显降低(P<0.05或P<0.01),着床前死亡率和着床后死亡率显著升高(P<0.01);与各剂量组雄性大鼠交配的雌鼠在平均黄体数和吸收胎数上差异无显著性(P>0.05)。结论:雄性大鼠隔日尾静脉注射给药28d0.75mg·kg-1剂量的MC004,对生殖系统产生明显毒性,导致雄性大鼠生育力降低。
Objective:To study the toxic effects of MC004 on fertility of male rats. Methods:Healthy and mature Wistar rats (n = 48) were randomly divided into four groups (12 rats in each group). The rats in control group were intravenously injected with normal saline, and the rats in other groups were administered with MC004 at doses of 0.25,0.50 and 0.75 mg·kg^-1, respectively. All rats were injected once every two days. All the 48 rats were sacrificed after 28 days. The clinical symptoms, body weight, reproductive ability and the pregnancy index were evaluated. Results : At the dose of 0.75 mg· kg^-1, the fertility index and the pregnancy index were significantly decreased. There was no difference between the control dams and the dams mated with MC004-treated males,in the mating indices,the mean number of corpus lutea, and the mean number of absorption fetuses. However,there was a significant decrease in the weight of uterus,placenta,ovary,the mean number of implants and the mean number of alive fetuses,and an increase in the mean percentage of preimplantation and the mean percentage of postimplantation as compared with the control group. Conclusion: MCO04 has obvious reproductive toxicities to puberty male after injection of 0. 75 mg. kg^-1, once every two days.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2009年第23期2215-2218,共4页
Chinese Journal of New Drugs
基金
重大新药创制科技重大专项(2008ZX09305-003)
北京市科委科技计划"创新药物研究开发"项目(D07080201330721)
北京市自然科学基金(7092079)
北京市新药研发系统创新服务平台建设(Z08030203080818)