目的 运用网络药理学技术探讨逍遥散与文拉法辛联用抗抑郁的作用机制。方法 通过TCMSP、PubChem、OMIM、GeneCards以及UniProt等数据库获得逍遥散和文拉法辛治疗抑郁症的作用靶点；利用STRING网站得到蛋白互作网络；并通过Metascape网站对潜在作用靶点进行富集分析；使用Cytoscape软件绘制“靶点-成分-通路”可视化网络图。结果 逍遥散主要通过芍药苷、刺槐素、儿茶素、槲皮素等化学成分和文拉法辛联合作用发挥抗抑郁作用。逍遥散和文拉法辛治疗抑郁症的相关靶点共208个，主要为酪氨酸蛋白激酶（SRC）、信号转导和转录激活器3（STAT3）、转录因子AP-1（JUN）、丝裂原活化蛋白激酶3（MAPK3）等。这些主要靶点作用于糖尿病并发症中的AGE-RAGE信号通路（AGE-RAGE signaling pathway in diabetic complications）、癌症通路（pathways in cancer）等43条通路，调节对受损的应答（response to wounding）、对无机物的应答（response to inorganic substance）以及细胞成分运动的正向调节（positive regulation of cellular component movement）、血液循环（blood circulation）和有机羟基化合物代谢过程（organic hydroxy compound metabolic process）等生物学过程发挥抗抑郁作用。结论 逍遥散与文拉法辛联用通过多靶点、多通路发挥抗抑郁作用，利用网络药理学预测中西药联合治疗疾病的作用机制值得深入探讨。

Objectives To investigate the anti-depressant mechanisms of Xiaoyao San combined with venlafaxine by using network pharmacological techniques. Methods The targets of Xiaoyao San and venlafaxine on depression were obtained through the TCMSP database, PubChem database, OMIM database, GeneCards database, and Uniprot database. The protein interaction network was obtained by using the String website. The potential targets were enriched through the Metascape website. Cytoscape software was used to draw the visual network diagram of "target-component-pathway". Results In combination of venlafaxine, Xiaoyao San exhibited anti-depression effects through paeoniflorin, robinin, catechin, quercetin and other chemical constituents. There were 208 related targets of Xiaoyao San and venlafaxine in the treatment of depression, mainly including tyrosine protein kinase, signal transducers and transcriptional activators 3, transcription factor AP-1, mitogen-activated protein kinase 3. These main targets play an anti-depressant role via regulating 43 pathways, such as AGE-RAGE signaling pathway in diabetic complications, pathways in cancer, and influencing biological processes, such as response to wounding, response to inorganic substance, positive regulation of cellular component movement, blood circulation, organic hydroxy compound metabolic process. Conclusions The combination of Xiaoyao San and venlafaxine plays an anti-depressant role through multi-targets and multi-pathways. It is worthy to deeply explore the underlying mechanisms of the combined effects of Chinese and western medicines by network pharmacology.

R285.5

国家自然科学基金青年基金项目（81803962）；山西省留学回国人员科技活动择优资助项目（20200013）