目的 基于气相色谱-质谱联用技术（gas chromatography-mass spectrometry，GC-MS）、网络药理学及分子对接技术识别并探究醒脑静注射液入脑成分及其治疗脑缺血损伤的作用机制，为其药效物质基础研究提供参考依据。方法 调研文献获取醒脑静入脑成分并采用GC-MS技术对其入脑成分进行补充，在此基础上，利用中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）和Swiss数据库对醒脑静注射液入脑成分进行靶点预测；同时通过CTD、OMIM、GeneCards等数据库获取脑缺血靶点；进一步利用OmicShare平台对药物与脑缺血共有靶点进行基因本体（gene ontology，GO）、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；采用String数据库和Cytoscape 3.7.2软件构建蛋白互作（protein-protein interaction，PPI）网络图及"入脑成分-脑缺血靶点-通路"网络图，并对入脑成分与核心靶点进行分子对接验证。结果 鉴定出龙脑、麝香酮、樟脑、莪术二酮等13种醒脑静注射液入脑成分；通过网络药理学技术得到93个醒脑静注射液治疗脑缺血的作用靶点，包括MPO、PPARG、HMOX1、MMP2等。通路富集分析表明神经营养蛋白信号通路（neurotrophin signaling pathway）、雌激素信号通路（estrogen signaling pathway）及血管内皮生长因子信号通路（vascular endothelial growth factor signaling pathway）等可能是醒脑静注射液发挥抗脑缺血损伤的主要途径。通过分子对接技术验证得出代表性成分（栀子苷、莪术二酮、麝香酮）与治疗脑缺血潜在靶点具有较好的亲和。结论 明确了醒脑静注射液的入脑成分，预测了入脑成分治疗脑缺血损伤的作用机制并初步验证了其靶点，为深入阐明醒脑静注射液的药效物质基础及作用机制提供了实验及理论依据。

Objective To identify and explore the anti-cerebral ischemic injury mechanism of the brain absorption components of Xingnaojing Injection (醒脑静注射液) by using gas chromatography-mass spectrometry technology (GC-MS), network pharmacology and molecular docking technology, and provide some evidences for the research of its pharmacodynamic substances. Methods In this study, the brain absorption components of Xingnaojing Injection was investigated through the literature mining and GC-MS technology was used to supplement their components. On this basis, TCMSP and Swiss databases were used to predict the targets of the brain absorption components of Xingnaojing Injection, while the targets of cerebral ischemia were screened through CTD, OMIM, GeneCards and other databases. Next, the KEGG pathway annotation analysis and GO enrichment analysis on common targets of drugs and cerebral ischemia were carried out through OmicShare platform. String database and Cytoscape 3.7.2 software were further used to construct separately protein-protein interaction network diagram and "the brain absorption components-cerebral ischemia targets-pathways" network diagram, and molecular docking was used to verify the brain absorption components and core targets. Results A total of 13 brain absorption components were identified in Xingnaojing Injection, such as borneol, muscone, camphor and curdione. And 93 Xingnaojing Injection targets of anti-cerebral ischemia were found through network pharmacology technology, including MPO, PPARG, HMOX1, MMP2, etc. Pathway enrichment analysis revealed that neurotrophin signaling pathway, estrogen signaling pathway and VEGF signaling pathway might be the main action pathways of anti-cerebral ischemia injury of Xingnaojing Injection. The results of molecular docking showed that representative components (geniposide, curdione, and muscone etc.) had good affinity with potential targets of anti-cerebral ischemia. Conclusion In this study, the brain absorption components of Xingnaojing Injection were clarified, and the mechanism of the brain absorption components treating anti-cerebral ischemia injury was predicted and its targets were preliminarily verified. The results provided experimental and theoretical basis for further clarifying the pharmacodynamic material basis and mechanism of Xingnaojing Injection.

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教育部“创新团队发展计划”项目（IRT_15R55）；国家自然科学基金面上项目（31971143）；陕西省重点研发计划国际合作项目（2017KW-055）