不同剂量炔雌醚对小鼠器官鲜重、繁殖生理和肝肠CYP3A4酶含量的影响  

Effect of different doses of quinestrol on organs,sperm density,reproductive hormones and CYP3A4 enzyme levels of male and female mice

作　　者：王宇杰 刘雨杭 秦姣 刘郁桐 聂海燕[1] 刘全生 WANG Yujie;LIU Yuhang;QIN Jiao;LIU Yutong;NIE Haiyan;LIU Quansheng(College of Life Science and Technology,Central South University of Forestry and Technology,Changsha 410004,China;Guangdong Key Laboratory of Animal Conservation and Resource Utilization,Guangdong Public Laboratory of Wild Animal Conservation and Utilization,Institute of Zoology,Guangdong Academy of Sciences,Guangzhou 510260,China;College of Agriculture,South China Agriculture University,Guangzhou 510642,China)

机构地区：[1]中南林业科技大学生命科学与技术学院,长沙410004 [2]广东省科学院动物研究所,广东省动物保护与资源利用重点实验室,广东省野生动物保护与利用公共实验室,广州510260 [3]华南农业大学农学院,广州510642

出　　处：《兽类学报》2021年第2期202-213,共12页Acta Theriologica Sinica

基　　金：广东省科技计划项目(2016A020210054);广东省科学院科技发展专项(2018GDASCX-0107);研究生培养基金(GIABR-pyjj201805)。

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。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

关 键 词：CYP3A4酶 不育控制 激素 小鼠 炔雌醚 

分 类 号：Q494[生物学—生理学]