围绝经期综合征已严重影响妇女身心健康，中医药防治日益迫切。课题组前期研究发现：欢乐宁方以“滋补心肾、除烦安神”为治疗大法，能明显改善心肾不交型围绝经期患者的潮热汗出、失眠多梦、抑郁等症状，但作用机制不明；前期发现欢乐宁对Kisspeptin神经元有重要调控作用，而最新研究证明Notch/Hes信号通路是指导Kisspeptin神经元分化的重要分子开关。为此，我们提出欢乐宁可能通过Notch信号调控Kisspeptin神经元调节内分泌，从而治疗围绝经期综合征。本项目拟在成功建立心肾不交型围绝经期综合征病证结合模型的基础上，揭示心肾不交证与围绝经期综合征的关联性，并观察欢乐宁方对模型小鼠下丘脑Notch1/Hes1通路及通过Cre-loxP技术观测药物对下丘脑Notch1的调控，探讨欢乐宁方治疗心肾不交型围绝经期综合征的作用机制，为开发治疗围绝经期综合征的药物提供新思路和药物靶点。

Perimenopausal syndrome has seriously affected women's physical and mental health,which is increasingly urgent of traditional Chinese medicine to prevent and treat.The previous study shows that Huanlening prescription,based on the therapeutic rule of nourishing heart and kidney incoordinationby, removing anxiety and calming the mind,can significantly improve the symptoms of hot flashes, sweating, insomnia, dreaminess and depression in patients suffered from perimenopausal syndrome with heart and kidney incoordination,but the mechanism was unknown.Previous studies have found that huanlening prescription plays an important role in the regulation of Kisspeptin neurons.And the.latest research proves that it is an important molecular switch of Notch/Hes signaling pathway to regulate the neuronal differentiation of Kisspeptin. Therefore,we think Huanlening prescription can regulate endocrine through Notch signaling of Kisspeptin neurons, so as to treat perimenopausal syndrome.This project aims to observe the relationship between heart and kidney incoordination and perimenopausal syndrome by successfully establishing the syndrome combination model of perimenopausal syndrome with heart and kidney incoordination. And to observe the regulation of Notch1 / Hes1 pathway in hypothalamus of model mice and the regulation of drug of Notch1 in hypothalamus throughCre-loxP technology.To clarify the mechanism of Huanlening prescription in treating perimenopausal syndrome with heart and kidney incoordination and to provide new ideas and drug targets for the development of drugs for the treatment of perimenopausal syndrome.