雷公藤多苷诱导小鼠睾丸生殖相关基因异常表达及补肾中药的干预作用

目的:探讨雷公藤多苷诱导小鼠睾丸生殖相关基因的表达及补肾中药的干预作用。方法:成年Balb/C雄性小鼠,以雷公藤多甙30 mg/(kg.d)灌胃3周,造成生殖减退模型。随后,分别予生理盐水0.25 ml/d、雷公藤多甙30 mg/(kg.d)、肉苁蓉煎液相当于生药10 g/(kg.d)]、熟地煎液相当于生药10 g/(kg.d)]、肉苁蓉、熟地等比例的煎液相当于生药20 g/(kg.d)]每日1次灌胃进行干预;另设肉苁蓉预处理组持续给予雷公藤多甙30 mg/(kg.d)和肉苁蓉煎液相当于生药10 g/(kg.d)],每日1次灌胃,灌胃3周。检测各组睾丸生殖相关基因Dzip1、Fas、c-jun、Wnt4的表达量的变化。结果:雷公藤模型小鼠Y染色体微缺失相关基因Dzip1表达下调,生殖细胞凋亡相关基因Fas表达上调,原癌基因c-jun表达上调,信号转导相关基因Wnt4表达上调,补肾中药干预后均有不同程度改善,其中以补益肾阳药物肉苁蓉与补益肾阴药物熟地联合应用效果最显著。结论:雷公藤多苷对生殖相关基因的表达有影响;补益肾阳药物肉苁蓉能够部分拮抗雷公藤生殖毒性,补益肾阴药物熟地亦表现出一定的拮抗雷公藤生殖毒性作用,联合应用肉苁蓉和熟地则加强了拮抗雷公藤生殖毒性的作用,揭示了阴中求阳、阴阳互根互用的现代药理基础。肉苁蓉有一定的预防雷公藤生殖毒性的作用。

GTW-induced abnormal expressions of testicular reproduction-related genes and intervention with kidney-tonifying Chinese herbs

Objective: To explore the abnormal expressions of testicular reproduction-related genes induced by glycosides of Tripterygium wilfordii(GTW) and the intervention with kidney-tonifying Chinese herbs.Methods: Adult Balb/C male mice were fed on GTW at 30 mg per kg per d for 3 weeks to establish a model of reproductive dysfunction.The model mice were divided into different groups to receive intragastrical administration of saline(0.25 ml/d),GTW(30 mg per kg per d),Cistanche(10 g per kg per d),Rehmannia(10 g per kg per d),and Rehmannia + Cistanche(20 g per kg per d),respectively,once a day for 3 weeks.And a Cistanches pretreatment group was treated with GTW(30 mg per kg per d) and Cistanche(10 g per kg per d) for the same length of time.Then we detected the changed expressions of testicular reproduction-related genes Dzip1,Fas,c-jun and Wnt4 in each group.Results: The model mice showed an obviously down-regulated expression of the Y chromosome microdeletion-related gene Dzip1,and up-regulated expressions of the germ cell apoptosis-related gene Fas,proto-oncogene c-jun,and signal transduction-related gene Wnt4.Intervention with Chinese herbs achieved different degrees of improvement of the mice’s reproductivity,and the most obvious efficacy was observed with the combined use of kidney-yang tonifying Cistanche and kidney-yin nourishing Rehmannia.Conclusion: GTW exerts significant impact on reproduction-related genes.Both the kidney-yang tonifying drug Cistanche and kidney-yin nourishing drug Rehmannia can counteract some of the reproductive toxicity of GTW,while the combination of the two can further enhance the effect.