目的 基于网络药理学和分子模拟对接技术探究苏合香丸治疗缺血性卒中的活性成分和作用机制。方法 通过中药系统药理学平台（TCMSP）和中医药综合数据库（TCMID）获取苏合香丸中15味药材的化学成分和作用靶点，并通过PubChem数据库和String平台进行靶点预测和收集，采用GeneCards和DisGeNET数据库获得缺血性卒中相关基因，两者取交集获得共有靶点，并经Cytoscape软件将结果可视化，通过网络拓扑算法获得核心化合物和核心靶点；通过String平台构建PPI网络获得苏合香丸治疗缺血性卒中的重要靶点，通过DAVID平台对重要靶点进行基因本体（gene ontology，GO）功能及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；使用Autodock Vina软件进行分子对接，验证网络分析结果。结果 苏合香丸的主要活性化合物66个，其中1，2，15，16-四氢丹参酮、荜茇壬二烯哌啶、去甲波尔定、乌药醚内酯等9个化合物可能是苏合香丸治疗缺血性卒中的核心成分；筛选出苏合香丸治疗缺血性卒中的重要靶点63个，核心靶点11个，其中IL10、ESR1、CXCL8以及CASP3是关键的核心靶点；GO功能富集分析和KEGG通路富集分析显示苏合香丸主要对机体炎症反应、NO生成、平滑肌细胞增殖、细胞凋亡以及机体对脂多糖、药物的细胞反应等生物过程进行调控，并且可能通过调控TNF信号通路、Toll样受体信号通路、HIF-1信号通路、PI3K-Akt信号通路、MAPK信号通路、FoxO信号通路以及神经营养因子信号通路等途径作用于缺血性卒中。结论 初步探究苏合香丸治疗缺血性卒中的潜在活性成分和可能的作用机制，为进一步阐明苏合香丸治疗缺血性卒中的药效物质、后期的深入开发研究提供了参考。

Objective To explore the active ingredients and mechanism of Suhexiang Pill in the treatment of ischemic stroke based on network pharmacology and molecular docking. Methods Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database(TCMID)were applied to obtain chemical components and potential targets of fifteen herbs in Suhexiang Pilll. The predicted targets of active compounds were collected from Pubchem database and STRING platform, Disease targets relating to ischemic stroke were screened out through GeneCards database and DisGeNET database, drug targets were integrated with disease targets, and intersection targets were exactly the potential action targets of Suhexiang Pill in treating ischemic stroke, Cytoscape software was used to construct the network of active ingredient-potential target genes, the key ingredients and core targets were selected based on topological parameters. A protein-protein interaction (PPI) network was constructed through the STRING platform and the core targets in the network were predicted, and the enrichment analyses of core targets were completed by DAVID database. Furthermore, a molecular docking method was used to verify the binding of the components with the main core targets using softwares such as Autodock Vina. Results There were 66 major active compounds in Suhexiang Pill, nine active compounds such as trijuganone B, pipernonaline, norboldine and linderane may be the main therapeutic ischemic stroke of Suhexiang Pill active ingredients. There were 63 core targets and 11 key targets in the treatment of ischemic stroke were obtained, IL10、ESR1、CXCL8 and CASP3 may be the main core targets of Suhexiang Pill in treating ischemic stroke. The results of GO enrichment analysis showed that the biological functions were mainly involved in the regulation of inflammatory response, nitric oxide biosynthetic process, smooth muscle cell proliferation, apoptosis process, response to lipopolysaccharide and response to drug. The results of KEGG pathway enrichment analysis showed that TNF signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway and Neurotrophin signaling pathway might be the key signaling pathways of Suhexiang Pill in treating ischemic stroke. Conclusion It is preliminarily explored the potential active ingredients and possible mechanisms of Suhexiang Pill in treatment of ischemic stroke, and provides reference for further elucidation of the pharmacological effects of Suhexiang Pill against ischemic stroke, subsequent development research.

R285.5

国家自然科学青年基金项目（81703870）