青盐方治疗围绝经期焦虑症的网络分析及实验验证  

Network analysis and experimental verification of Qingyan Formula in treatment of perimenopausal anxiety disorder

作　　者：赵元 郑红霞 徐颖[1] 林娜[1] ZHAO Yuan;ZHENG Hong-xia;XU Ying;LIN Na(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]深圳市中医院深圳市医院中药制剂研究重点实验室,广东深圳518033

出　　处：《中国中药杂志》2020年第17期4129-4139,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81774203,81573632)。

摘　　要：基于网络药理学方法挖掘青盐方(Qingyan Formula,QYF)治疗围绝经期焦虑症(perimenopausal anxiety disorder,PAD)的潜能并进行药效学的实验验证。首先利用中药系统药理数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索青盐方中的药物化学成分,然后利用中医药整合药理学网络计算研究平台(Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine,TCMIP)v2.0和Swiss Target Prediction数据库筛选药物靶标,通过GeneCards和OMIM数据库查询PAD相关的靶标,筛选QYF和PAD的共有靶标,然后进行信号通路的富集分析;采用旷场试验和O迷宫试验验证QYF治疗PAD焦虑大鼠的药效学作用,并检测血清神经递质水平。结果显示,QYF可能发挥作用的类固醇激素合成、卵巢类固醇生成、雌激素信号通路等调控类固醇激素类信号通路,色氨酸代谢通路、Toll样受体信号通路、TGF-β信号通路等调控中枢神经递质,NF-κB信号通路、Apelin信号通路、MAPK信号通路、TNF信号通路、FOXO信号通路等调控炎症反应的信号通路均与PAD有关,说明QYF可能具有防治PAD的作用。青盐方70%乙醇提取物(Qingyan Formula 70%ethanol extract,QYFE)能延长去卵巢(ovariectomized,OVX)焦虑大鼠在旷场试验中央场的活动时间和活动距离,增加OVX焦虑大鼠在O迷宫试验中开臂区域的持续时间和活动距离,具有抗焦虑作用,且升高OVX焦虑大鼠血清5-羟色胺(5-hydroxytryptamine,5-HT)、γ氨基丁酸(gamma aminobutyric acid,GABA)水平,显著降低谷氨酸(glutamate,Glu)、去甲肾上腺素(norepinephrine,NA)水平,逆转OVX引起的兴奋性/抑制性递质平衡的紊乱,可能与其缓解OVX大鼠焦虑障碍有关。This paper aims to explore the potential of Qingyan Formula(QYF)in the treatment of perimenopausal anxiety disorder(PAD)by network pharmacological method,and verify the pharmacodynamics and mechanism by using animal experiments.First,Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)was used to retrieve the active components of QYF.Then the potential drug targets were screened with use of Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP)v2.0 and Swiss Target Prediction database.Targets related to PAD were retrieved and screened from the OMIM database and GeneCards database.The intersection targets of QYF and PAD were screened out,and then the enrichment analysis of the signal pathways was conducted.Open field experiments and the O maze experiment were used to verify the pharmacodynamic effect of QYF in the treatment of PAD rats,and the serum neurotransmitter level was detected.The results showed that QYF may be have the function of regulating steroid hormone signaling pathways such as steroid hormone synthesis,ovarian steroidogenesis and estrogen signaling pathways,regulating central neurotransmitters signaling pathways including tryptophan metabolism pathways,Toll-like receptor signaling pathways,TGF-βsignaling pathway and regulating inflammatory response pathways including NF-κB signaling pathway,Apelin signaling pathway,MAPK signaling pathway,TNF signaling pathway,and FOXO signaling pathway.All of the signaling pathways were related to PAD,which indicated that QYF may have the role of treating PAD.Qingyan Formula 70%ethanol extract(QYFE)revealed anxiolytic effects by extending the activity time and distance of anxious ovariectomized(OVX)rats in the central field of open field experiments,and increasing the duration and activity distance of anxious OVX rats in the open arm area in O maze experiments.QYFE increased serum serotonin/5-hydroxytryptamine(5-HT),and gamma aminobutyric acid(GABA)levels in anxious OVX rats,

关 键 词：青盐方 围绝经期焦虑症 网络药理学 旷场试验 O迷宫试验 

分 类 号：R285.5[医药卫生—中药学]