目的:研究使用不同时间和剂量的雷公藤多甙(GTW)对昆明小鼠怀孕率的影响及肉苁蓉干预和停用GTW后的自愈倾向。方法:将90只成年雄性昆明鼠随机分为9组(每组10只)。对照组给予1%羧甲基纤维素(CMC)溶液;GTW各组分别给予45.0、30.0、22.5、15.0、7.5mg/(kg·d)GTW混悬液;肉苁蓉各组分别给予30.0、7.5mg/(kg·d)GTW混悬液;停药组给予30.0mg/(kg·d)GTW混悬液。以上各组先灌胃20d,20d后与成年雌鼠1:2合笼7d。第28d起GTW各组按原剂量继续给药;肉苁蓉各组给原剂量GTW混悬液的同时分别给10.0、2.5g/(kg·d)肉苁蓉煎液;停药组停GTW,改为1%CMC溶液。20d后再次合笼7d。每次合笼后观察雌鼠怀孕率。结果:随着GTW给药时间的延长和剂量的增加,雌鼠怀孕率呈下降趋势。GTW45.0mg/(kg·d)组给药40d后怀孕率降为0%(P〈0.01)。肉苁蓉10.0g/(kg·d)组怀孕率由20d时的25%上升到40d时的55%。停药组怀孕率由25%上升到56%,与对照组比较,差异无显著性(P〉0.05)。结论:GTW对雄性小鼠的生殖毒性呈时间和剂量依赖性。肉苁蓉可以改善GTW对雄鼠生殖系统的抑制作用,提高雌鼠的怀孕率。停用GTW20d,怀孕率可以基本恢复正常。
Objective : To study the impact of glycosides of tripterygium wilfordii (GTW) on fertility, and the reversibility of this im- pact following intervention with cistanche deserticola (CD) and after withdrawal of GTW. Methods : Ninety adult male KM mice were equally and randomly divided into 9 groups: 5 GTW groups, treated with GTW at 45.0, 30.0, 22.5, 15 and 7.5 mg/kg · d, respectively, :2 CD groups, administered GTW at 30.0 and 7.5 mg/kg · d, respectively, a drug withdrawal group, given GTW at 30.0 mg/ kg · d, and a control group, given 1% CMC solution, all intragastrically for 20 days. Then they were mated with female mice at the ratio of 1 : 2 for 7 days, followed by another 20 days of medication, the GTW groups at the same doses, the CD groups given CD additionally at 10.0 g/kg · d and 2.5 g/kg · d respectively, and the withdrawal group given 1% CMC solution only. Again they were mated with the same females, and the pregnancy rate was observed after each mating. Results: The pregnancy rate dropped with the increase of the dose and medication time of GTW, which was 0% at 40 d in the 45.0 mg/kg · d GTW group ( P 〈 0.01 ), but rose from 25% at 20 d to 55% at 40 d in the 10.0 g/kg · d CD group, and from 25% at 20 d to 56 % at 40 d in the withdrawal group. Conclusion: The reproductive toxicity of GTW acts on male mice in a time- and dose-dependent manner, which can be reduced by Cistanche deserticola. The fertility of the male mice can be restored to normal 20 days after the cessation of GTW.