目的 结合数据挖掘、网络药理学、分子对接方法及临床观察，探究贾跃进临床治疗女性失眠症的用药规律及作用机制。方法 首先使用古今医案云平台V2.2.3将贾跃进门诊近5年中药治疗女性失眠症的处方进行药物频次、属性统计以及关联、聚类和复杂网络分析，得出核心组方；再将核心组方运用TCMSP、GEO等数据库得到各药物有效成分的靶点与疾病靶点并取交集，利用CytoscapeV3.8.0及其插件构建疾病-药物-成分-靶点、蛋白互作网络，并进行基因本体论（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析；然后通过分析以上所得的2个网络获取其关键成分及靶点并进行分子对接；最终以核心组方为治疗组，网络药理学预测结果为主要观察指标进行临床研究验证。结果 数据挖掘纳入验案221例，方剂258首，涉及中药139味；药性以平、温、微寒为多；药味以甘、辛、苦为主；药物主要归肝、脾经；通过药物关联、聚类和复杂网络分析综合得出11味药物的核心组方。网络药理学共获得核心组方有效成分65种，相关靶点490个，交集靶点142个，关键成分有β-谷甾醇和豆甾醇等，关键靶点聚类有神经递质类及细胞因子类等。GO功能富集分析结果显示，可能与代谢过程、免疫系统过程和信号过程有关；KEGG通路富集分析结果显示，可能与神经活性配体-受体相互作用、血清素能突触、多巴胺能突触等有关；分子对接较好的靶点为蛋白激酶Bα（protein kinase Bα，AKT1）、5-羟色胺受体1A（5-hydroxytryptamine receptor 1A，HTR1A）、多巴胺受体D2（dopamine receptor D2，DRD2）。临床研究显示，核心组方治疗组患者血清中褪黑素（melatonin，MT）水平显著升高，5-羟色胺（5-hydroxytryptamine，5-HT）、多巴胺（dopamine，DA）水平显著降低（P<0.05）。结论 贾跃进治疗女性失眠症的核心组方包括茯苓、白术、合欢皮、柴胡、香附、白芍、龙骨、当归、牡丹皮、栀子、白茅根，其主要通过多成分、多靶点调控MT、5-HT、DA而实现，对临床相关研究及对女性失眠症的治疗有一定指导意义。

Objective To explore the medication rule and mechanism of traditional Chinese medicine (TCM) doctor Jia Yuejin in treating female insomnia disorder (FID) by methods of data mining, network pharmacology, molecular docking and clinical trial. Methods First of all, the medication rule and core prescription was obtained by analyzing the drug frequency and attribute statistics as well as correlation, clustering and complex network on the prescriptions of TCM for FID in Jia Yue-jin’s Clinic in the past five years with the help of cloud platform of ancient and modern medical cases (V2.2.3). Then, the intersection between the targets of active components of each drug and the disease targets were obtained by using databases such as TCMSP and GEO; The disease-drug-component-target and protein-protein interaction networks were constructed by Cytoscape 3.8.0 and its plug-ins, and performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Then the key components and targets were obtained by analyzing the above two networks and molecular docking was carried out. Finally, the core prescription was used as the treatment group, and the result predicted by network pharmacological prediction results was set as the main observation index for clinical trial verification. Results A total of 221 clinical cases, 258 prescriptions and 139 drugs were obtained in total by data mining; The most common drug properties were flat, warm, slightly cold; The main tastes were sweet, pungent and bitter, and the meridians were mainly concentrated in the two meridians of liver and spleen; The core prescription which consists of 11 drugs was obtained through analysis of drug association, cluster and complex network. A total of 65 active ingredients, 490 related targets, 142 intersectional genes of the core prescription were obtained, the key ingredients included β-sitosterol, stigmasterol, etc., and the key target clusters include cytokines and neurotransmitters, etc. GO functional enrichment analysis showed that it may be related to metabolic processes, immune system processes and signal processes. KEGG pathway enrichment analysis showed that it may be related to neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse and so on; The good targets for molecular docking were protein kinase Bα (AKT1), 5-hydroxytryptamine receptor 1A (HTR1A) and dopamine receptor D2 (DRD2). Clinical studies showed that the serum levels of melatonin (MT) and 5-hydroxytryptamine (5-HT) and dopamine (DA) were significantly decreased in the core prescription group (P < 0.05). Conclusion The core prescription in treating FID by Jia Yuejin includes Fuling (Poria), Baizhu (Atractylodis Macrocephalae Rhizoma), Hehuanpi (Albiziae Cortex), Chaihu (Bupleuri Radix), Xiangfu (Cyperi Rhizoma), Baishao (Paeoniae Radix Alba), Longgu (dragon bone), Danggui (Angelicae Sinensis Radix), Mudanpi (Moutan Cortex), Zhizi (Gardeniae Fructus), Baimaogen (Imperatae Rhizoma), which mainly regulate MT, 5-HT and DA through multi-ingredient and multi-target ways. This conclusion has certain guiding significance for clinical related research and the treatment of FID.

R285.64

国家自然科学基金面上项目（81573853）；山西省科技厅应用基础研究项目（201801D221430）；山西省中医药管理局科研课题（2019ZYYC025）；国家中医药管理局全国老中医药专家传承工作室建设项目—贾跃进老中医药专家传承工作室（M020011190M）