Abstract: To investigate the effects of varied-dose quinestrol on the weight of organs,concentration of reproductive hormones in serum,and content of CYP3A4 enzyme in intestine and liver,Swiss mice were treated with 0.008 mg/kg,0.04 mg/kg,0.2 mg/kg,1.0 mg/kg,and 5.0 mg/kg of quinestrol for 3 consecutive days and dissected on the day 7 after the first dose.In female mice,the liver weight increased with the dose increasing,and the liver weight of mice in the dose of 5.0 mg/kg increased 89.7% than that of the control.Small intestine,kidney and spleen were changed significantly,but there was no evident dose effect.The uterus showed different degrees of edema in female mice treated by 0.2 mg/kg,1.0 mg/kg,and 5.0 mg/kg of quinestrol.The luteinizing hormone and estradiol concentrations in serum were no significant change among varied groups of female mice.However,the follicle-stimulating hormone concentration significantly increased in female mice treated with 1.0 mg/kg quinestrol compared with the control.CYP3A4 enzyme content of liver in female treated by 1.0 mg/kg and 5.0 mg/kg of quinestrol increased significantly by 59.1% and 102.9%,respectively.In male mice,quinestrol at different doses showed a significant impact on the liver and spleen,which increased by 23.3% and 130% in mice treated by 5.0 mg/kg of quinestrol,but no significant change was observed in small intestine and kidney.Quinestrol had no significant dose effect on testes,however epididymis decreased significantly in male treated with 5.0 mg/kg quinestrol.Sperm density and total sperm count decreased by 43.9% and 70.5% at the dose of 1.0 mg/kg and 5.0 mg/kg compared with the control male,respectively.Luteinizing hormone and testosterone concentration in serum decreased significantly in high dosage groups.CYP3A4 content in per g tissues and total content in liver increased by 7.1% and 30% in male treated with 5 mg/kg quinestrol,respectively.In conclusion,quinestrol has inhibitory effects on reproduction of male and female mice,but the effective dose on female is lower than male.The response of liver and CYP3A4 to quinestrol in female was more sensitive than that in male,which indicated more quickly metabolism speed to quinestrol in female mice.

Key words: CYP3A4, Fertility control, Hormone, Mice, Quinestrol

摘要： 为探究不同剂量炔雌醚对小鼠器官、激素和肝肠药解酶的影响，分别以0.008 mg/kg、0.04 mg/kg、0.2 mg/kg、1.0 mg/kg和5.0 mg/kg的炔雌醚油溶液连续3 d灌胃小鼠，首次给药7 d后解剖取材，检测其器官鲜重、雄鼠精子数量、血清中激素浓度、小肠和肝脏中CYP3A4酶含量的变化。结果发现：雌鼠肝脏鲜重随剂量增加而增大，5.0 mg/kg组比对照组增大89.7%；雌鼠小肠、肾脏和脾脏出现不同程度变化，但无明显剂量效应；0.2 mg/kg以上剂量炔雌醚导致雌鼠子宫不同程度的水肿；炔雌醚对雌鼠血清中雌二醇和促黄体素浓度无显著影响，仅1.0 mg/kg组雌鼠血清中卵泡生成素浓度较对照组显著升高；1.0 mg/kg和5.0 mg/kg组雌鼠肝脏中CYP3A4酶总含量较对照组分别显著增加59.1%和102.9%。不同剂量炔雌醚对雄鼠肝脏和脾脏鲜重影响显著，5.0 mg/kg剂量组肝脏和脾脏鲜重较对照组分别增大23.3%和130%，但小肠和肾脏无明显剂量效应；不同剂量炔雌醚对雄鼠睾丸鲜重无显著影响，附睾仅有5.0 mg/kg组较对照组显著减小；1.0 mg/kg和5.0 mg/kg组的精子密度和精子总数分别较对照组降低43.9%和70.5%；高剂量炔雌醚使血清中促黄体素和睾酮浓度均显著降低；5.0 mg/kg组雄鼠肝脏CYP3A4酶单位组织含量和总含量较对照组分别升高7.1%和30%。总之，炔雌醚对雌雄小鼠的繁殖均有抑制作用，但最低有效剂量不同，雌性有效剂量更低，而雌性肝脏及CYP3A4酶对炔雌醚的反应显著强于雄性，提示雌鼠肝脏对炔雌醚的代谢更快。

关键词: CYP3A4酶, 不育控制, 激素, 小鼠, 炔雌醚