基于临床数据探讨贾跃进老中医治疗肝郁化火型失眠症的机制

Exploration of Mechanism of Jia Yuejin′s Treatment of Insomnia Disorder of Type of Liver Depression Transforming into Fire Based on Clinical Data

目的通过对贾跃进老中医临床病案数据的分析探究其临床治疗肝郁化火型失眠症的用药规律与作用机制。方法首先使用古今医案云平台网页版将贾跃进教授门诊近五年中药治疗肝郁化火型失眠症的处方进行药物频次、属性的统计以及关联、聚类和复杂网络分析,得出核心药物组成。再将核心药物组成运用TCMSP、CNKI、GeneCards等数据库收集其各药物活性成分的靶点与疾病靶点并取二者交集,利用CytoscapeV3.6.2及STRING、Metascape等平台构建疾病-药物-成分-靶点网络、蛋白相互作用网络并进行GO和KEGG通路富集分析。最终以核心药物组成为治疗组,网络药理学预测结果为观察指标进行临床研究验证。结果①数据挖掘纳入方剂404首,涉及中药150味;药性以平、温、微寒为多;药味以甘、辛、苦为主;药物主要归:肝、脾等经;通过药物关联、聚类和复杂网络分析综合得出11味药物的核心药物组成。②网络药理学共得核心药物组成活性成分65种,相关靶点490个,交集靶点142个,其主要靶点包括:细胞因子类、神经递质类等;③GO功能富集分析结果主要有:突触信号传送、神经递质受体活性;KEGG通路富集分析结果主要有: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。④临床观察可以得出核心药物组成治疗组患者血清中5羟色胺(5-HT)、多巴胺(DA)含量显著降低(P<0.05),与网络药理学预测的神经递质结果基本相符。结论得出贾跃进治疗肝郁化火型失眠症主要利用核心药组通过多成分、多靶点调控5-HT、DA两类神经递质而实现,对于临床应用具有一定指导意义。

Objective To explore the medication rules and action mechanisms of Jia Yuejin in the treatment of insomnia disorder of liver depression transforming into fire syndrome based on clinical data. Methods First, we obtained the medication rules and core prescription by analyzing the statistics of frequency, properties and analysis of correlation,clustering, and complex network of prescriptions for the treatment of insomnia disorder of liver depression transforming into fire syndrome from the outpatient service of Professor Jia in the past five years with the help of cloud platform of ancient and modern medical cases. Then we obtained the targets of active ingredients of each drug of the core prescription and disease targets and took the intersection by virtue of TCMSP, CNKI, Genecards and other databases,made use of Cytoscape V3.6.2 and platforms of STRING and Metascap to construct disease-drug-ingredient-target and protein-protein interaction networks and performed GO and KEGG pathway enrichment analysis. Finally, the core prescription was used as the treatment group, and the network pharmacology prediction result was the main observation index for clinical research verification. Results(1) 404 prescriptions and 150 drugs were obtained in total by data mining;The most common drug properties were calm, warm, slightly cold;The main flavors were sweet, pungent and bitter, and the meridian was mainly concentrated in the two meridians of liver and spleen;The core prescription which consists of 11 drugs was obtained through analysis of drug correlation, clustering and complex network.(2) A total of 65 effective ingredients, 490 related targets, 142 intersectional genes of the core prescription were obtained, and the key ingredients included cytokines and neurotransmitters, etc.;(3) GO enrichment analysis results mainly included metabolic process, immune system process and signaling process;KEGG pathway enrichment analysis results mainly included neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, etc.(4) Clinical research could conclude that the serum 5-HT and DA levels of patients in the core prescription treatment group were significantly reduced(P< 0.05), which was basically consistent with the neurotransmitter results predicted by network pharmacology.Conclusion It is concluded that Professor Jia’s treatment of insomnia disorder of liver depression transforming into fire syndrome is mainly achieved through multi-component and multi-target regulation of 5-HT and DA neurotransmitters,which certain guiding significance for clinical application.