目的 运用网络药理学分析方法，明确柴胡桂枝干姜汤治疗失眠的作用机制。方法 运用TCMSP、TCMID数据库锁定柴胡桂枝干姜汤7味药的药物靶标，TTD、DrugBank、PubMed数据库查找失眠的疾病靶点，构建"疾病-方剂-靶点"网络，用STRING和Cytoscape分析软件对其关键靶点进行富集分析，明确作用机制。结果 柴胡桂枝干姜汤蛋白质-蛋白质相互作用（PPI）网络包含靶标640个，失眠的PPI网络包括靶标175个，富集分析得29个关键靶标和其间80条互作关系；GO富集分析及KEGG途径分析结果显示柴胡桂枝干姜汤中柴胡皂苷a、柴胡皂苷d、槲皮素、碳酸钙、6-姜辣醇、山柰酚、汉黄芩素等171个活性成分主要通过CACNA1C、GABRA1、GABRA2、GABRB3、GABRA3等29个关键靶标及突触信号传导、膜电位的调节、G蛋白偶联受体信号通路等生物过程，神经递质受体活性、离子门控通道活动、GABA-A受体活性等分子功能，质膜、突触等细胞组成作用于神经活性配体-受体相互作用、逆行内源性大麻素信号传导、5-羟色胺能突触等多条作用通路发挥治疗失眠作用。结论 柴胡皂苷a、柴胡皂苷d等171个活性成分是柴胡桂枝干姜汤治疗失眠的药效物质基础，神经活性配体-受体相互作用等通路和CACNA1C等29个靶标构成了其发挥"疏肝健脾、调和阴阳"的功效作用网络，为临床合理运用柴胡桂枝干姜汤治疗失眠提供了网络药理学证据。

Objective To investigate the mechanisms of effects of Chaihu Guizhi Ganjiang Decoction in the treatment of insomnia by using network pharmacology methods. Methods TCMSP and TCMID were used to lock the targets of seven herbs in Chaihu Guizhi Ganjiang Decoction. TTD, DrugBank, and PubMed were used to search targets of insomnia and construct a "disease-prescription-target" network. STRING and Cytoscape were used to perform enrichment analysis and clarify the mechanism of core targets in the network. Results The PPI network of Chaihu Guizhi Ganjiang Decoction contained 640 targets and the PPI network of insomnia included 175 targets. A total of 29 core targets and 80 interactions were found after enrichment analysis between two PPI networks. After GO enrichment analysis and KEGG pathway analysis of 29 key targets, we found that 171 active ingredients in Chaihu Guizhi Ganjiang Decoction such as saikosaponin a, saikosaponin d, quercetin, calcium carbonate, 6-gingerol, kaempferol, and wogonin, which played a role in the treatment of insomnia mainly through 29 core targets such as CACNA1C, GABRA1, GABRA2, GABRB3, GABRA3, with biological processes such as target and synaptic signaling, regulation of membrane potential, G-protein coupled receptor signaling pathway, and molecular functions such as neurotransmitter receptor activity, ion-gated channel activity, GABA-A receptor activity, and functional pathways composed by plasmalemma, synapse, and other cells such as neural active ligand-receptor interaction, retrograde endogenous cannabinoid signal transduction, and serotoninergic synapses. Conclusion The pharmacological substance basis for the treatment of insomnia was composed of 171 active ingredients such as saikosaponin a and saikosaponin d. The efficacy network of "soothing liver and invigorating spleen, regulating yin and yang" was constituted by several pathways like the neural active ligand-receptor interaction and 29 targets such as CACNA1C. Our results provide network pharmacological evidence for clinical rational use of Chaihu Guizhi Ganjiang Decoction for insomnia.

山东省重点研发计划（重大关键技术）项目（2016ZDJS07A21）；山东省重点研发计划项目（2017CXGC1301）；国家自然科学基金面上项目（81773997）；泰山学者工程专项经费项目（ts201511107）