| 摘要: |
| 目的：基于网络药理学和分子对接技术探讨固元健脑方防治高血压脑小血管病（HT-CSVD）的作用机制。方法：通过TCMSP及BATMAN-TCM和文献检索预测固元健脑方活性成分及靶点，通过GeneCards和OMIM数据库获取疾病靶点；使用Metascape构建蛋白质-蛋白质相互作用（PPI）网络，使用Metascape数据库分析基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路；应用Cytoscape 3.2.1进行可视化分析；采用Autodock Tools 1.5.7及Pymol 2.4.0对核心靶点和化合物进行分子对接。结果：筛选出固元健脑方治疗靶点277个，HT-CSVD靶点5173个，固元健脑方治疗HT-CSVD的靶点230个；其中连环蛋白1（CTNNB1）、丝裂原活化蛋白激酶（MAPK3）和B细胞淋巴瘤-2基因（Bcl-2）为关键基因靶点，槲皮素、山柰酚、木犀草素和5-羟甲基糠醛为关键活性成分；GO功能富集分析得到激素反应、循环系统进程、细胞对脂质的反应等条目。KEGG通路富集分析得到癌症途径、CAMP、细胞衰老、脂质与动脉粥样硬化、MAPK等信号通路；分子对接结果显示4种主要候选化合物与CTNNB1有较强的结合。结论：固元健脑方可通过多种活性成分、多个靶点、多条通路拮抗HT-CSVD的神经损伤而发挥治疗作用。 |
| 关键词: 高血压脑小血管病 固元健脑方 作用机制 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Guyuan Jiannao prescription in prevention and treatment of hypertensive cerebral small vascular disease：A study based on network pharmacology and molecular docking |
| JIANG Qiling,FANG Rui,ZHOU Yue |
| (Shaoyang University，Shaoyang 422000，Hunan，China;Hunan University of Chinese Medicine，Changsha 410208，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Guyuan Jiannao prescription in the prevention and treatment of hypertensive cerebral small vascular disease (HT-CSVD) based on network pharmacology and molecular docking.Methods：TCMSP，BATMAN-TCM，and related articles were searched to predict the active components of Guyuan Jiannao prescription and their targets，and GeneCards and OMIM databases were used to obtain disease targets；Metascape was used to construct a protein-protein interaction network，and Metascape database was used to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis；Cytoscape 3.2.1 was used for visual analysis；Autodock Tools 1.5.7 and Pymol 2.4.0 were used to perform molecular docking between core targets and compounds.Results：The above analyses obtained 277 therapeutic targets of Guyuan Jiannao prescription，5173 targets of HT-CSVD，and 230 targets for Guyuan Jiannao prescription in the treatment of HT-CSVD，among which CTNNB1，MAPK3，and Bcl-2 were the key gene targets，and quercetin，kaempferol，luteolin，and 5-hydroxymethyl furfural were the key active components.The GO functional enrichment analysis obtained the terms including response to hormone，circulatory system process，and cellular response to lipid.The KEGG pathway enrichment analysis obtained the signaling pathways such as cancer pathway，CAMP，cell senescence，lipids and atherosclerosis，and MAPK.Molecular docking showed that 4 main candidate compounds had a strong binding activity to CTNNB1.Conclusion：Guyuan Jiannao prescription exerts a therapeutic effect by antagonizing against nerve injury in HT-CSVD through multiple active components，targets，and pathways. |
| Key words: hypertensive cerebral small vascular disease Guyuan Jiannao prescription mechanism of action network pharmacology molecular docking |
