金匮肾气丸和六味地黄丸对正常小鼠生殖能力及其脑功能影响的比较OA
Comparative Study on Effect of Jingui Shenqiwan and Liuwei Dihuangwan on Reproductive Ability and Brain Function of Normal Mice
目的:探讨金匮肾气丸和六味地黄丸对正常小鼠生殖能力及脑功能的影响并对两药作用进行比较.方法:将雌雄鼠以 2∶1比例分为 7组,除正常组外,其余 6组分别为雌雄鼠均灌胃金匮肾气丸(3.0 g·kg-1)组,雌雄鼠均给六味地黄丸(4.5 g·kg-1)组,雄鼠给水雌鼠给金匮肾气丸组,雄鼠给水雌鼠给六味地黄丸组,雌鼠给水雄鼠给金匮肾气丸组,雌鼠给水雄鼠给六味地黄丸组.各组共给药14 d,然后以2∶1(雌/雄)比例合笼,检测受孕鼠数,计算受孕率,孕鼠继续给药待其自然分娩后观察新生小鼠,计算平均新生小鼠数,并检测子代小鼠的糖水偏好率及新生体识别指数等.实验结束时取小鼠胸腺脾脏称质量计算脏器系数,取脑和睾丸或卵巢做mRNA或蛋白表达.1%蔗糖水方法考察其脑奖赏系统的欣快感,新物体识别方法考察其记忆能力.实时荧光定量聚合酶链式反应(Real-time PCR)检测mRNA表达,蛋白免疫印迹法(Western blot)检测蛋白表达.结果:与正常组比较,连续给药14 d雌性和雄鼠均灌胃金匮肾气丸可以明显提高合笼2 d时雌鼠的受孕率(P<0.05),六味地黄丸有一定的趋势但无统计学意义.与正常组比较,金匮肾气丸还可以上调小鼠丘脑促性腺激素释放激素(GnRH)及睾丸生殖干细胞因子(SCF)和酪氨酸激酶受体(c-Kit)和卵巢生殖干细胞标志物小鼠RNA解旋酶同源物(Mvh)的基因表达和上调海马神经元的脑源性神经营养因子(BDNF)等影响神经元功能活动的蛋白表达(P<0.05),增强雄鼠蔗糖水偏好率(P<0.05).与正常组比较金匮肾气丸对子鼠的蔗糖水偏好率和新物体识别指数均明显提高(P<0.05),其机制与上调海马多巴胺D1受体(D1r),N-甲基-D-天冬氨酸受体(Nmdar)基因表达有关.与正常组比较金匮肾气丸和六味地黄丸均能上调子鼠海马糖皮质激素受体(GR)、BNDF、酪氨酸激酶受体B(TrkB)蛋白表达(P<0.05).结论:金匮肾气丸有明显促进正常小鼠受孕能力的作用,这不仅与促性腺激素释放有关,而且还与其调控脑功能有关,同时对子鼠的脑功能具有一定的调节作用.
Objective:To explore the effects of Jingui Shenqiwan(JSW)and Liuwei Dihuangwan(LDW)on the reproductive ability and brain function of normal mice and compare the actions of the two medications.Methods:Seven groups of female and male mice were divided at a ratio of 2∶1.Except for the control group,the other six groups were as follows:a group of both males and females receiving JSW(3.0 g·kg-1),a group of both males and females receiving LDW(4.5 g·kg-1),a group of males receiving water and females receiving JSW,a group of males receiving water while females receiving LDW,a group of females receiving water while males receiving JSW,and a group of females receiving water while males receiving LDW.Each group was administered the drug for 14 days and then caged together at a 2∶1(female∶male)ratio to detect the number of pregnant mice and calculate the pregnancy rate.Pregnant mice continued receiving the drug until they naturally gave birth,which was followed by the observation of newborn mice,calculation of their average number,and the measurement of the offspring's preference for sugar water and neonatal recognition index.At the end of the experiment,the weights of the thymus and spleen were measured to calculate the organ coefficients,and mRNA or protein expression was analyzed in the brain and testes or ovaries.A 1%sucrose solution was used to examine the euphoria of their brain reward systems,while novel object recognition test(NOR)was applied to assess their memory capabilities.mRNA expression was detected using real-time quantitative polymerase chain reaction(Real-time PCR)assay,and protein expression was analyzed with Western blot.Results:Compared with the control group,oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together(P<0.05),while LDW showed a trend but no statistical significance.Additionally,compared with the control group,JSW could upregulate the gene expression of gonadotropin-releasing hormone(GnRH)in the thalamus,as well as reproductive stem cell factor(SCF)and tyrosine kinase receptor(c-Kit)in the testes and reproductive stem cell marker mouse vasa homologue(MVH)in the ovaries,upregulate the expression of proteins influencing neuronal functional activity,such as brain-derived neurotrophic factor(BDNF),in hippocampal neurons(P<0.05),and enhance sucrose preference in male mice(P<0.05).Compared with the control group,JSW significantly increased sucrose preference and novel object recognition index in offspring mice(P<0.05),which was related to the upregulation of hippocampal dopamine D1 receptor(D1R)and N-methyl-D-aspartate receptor(Nmdar)gene expression.Compared with the control group,both JSW and LDW could upregulate the protein expression of glucocorticoid receptor(GR),BDNF,and tyrosine kinase receptor B(TrkB)in the hippocampus of offspring mice(P<0.05).Conclusion:JSW significantly enhances the reproductive ability of normal mice,which is not only related to the release of gonadotropin but also associated with its regulation of brain function.Additionally,JSW has a certain regulatory effect on the brain function of the offspring mice.
孙虹;雷帆;李成功;罗睿;胡时先;任宾;郝娟;丁怡;杜力军
中国医学科学院 中国协和医学院 药用植物研究所,北京 100094清华大学 生命科学学院,北京 100084新疆华春生物药业有限责任公司 药业研发中心,乌鲁木齐 830000中国医学科学院 中国协和医学院 药用植物研究所,北京 100094新疆华春生物药业有限责任公司 药业研发中心,乌鲁木齐 830000新疆华春生物药业有限责任公司 药业研发中心,乌鲁木齐 830000新疆华春生物药业有限责任公司 药业研发中心,乌鲁木齐 830000清华大学 生命科学学院,北京 100084清华大学 生命科学学院,北京 100084
医药卫生
金匮肾气丸六味地黄丸生殖脑功能促性腺激素释放激素
Jingui ShenqiwanLiuwei Dihuangwanreproductionbrain functiongonadotropin-releasing hormone
《中国实验方剂学杂志》 2026 (2)
1-14,14
国家"重大新药创制"科技重大专项(2018ZX09731020)清华大学科研发展基金项目(120001028)
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