| 摘要: |
| 目的：应用网络药理学及分子对接探讨桃红四物汤防治卒中后认知障碍（post-stroke cognitive impairment，PSCI）的作用机制。方法：利用中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacy Database and Analysis Platform，TCMSP）获取桃红四物汤的有效成分及对应靶点，通过人类基因数据库（Genecards Human Gene Database，GeneCards）和在线孟德尔遗传数据库（Online Mendelian Inheritance in Man，OMIM）数据库获得PSCI相关靶点;运用Venny 2.1.0软件获得药物与疾病的共同靶点;通过蛋白质相互作用 (Search Tool for the Retrieval of Interacting Genes/Proteins,STRING）数据库构建蛋白相互作用网络并筛选出潜在核心靶点。借助AutoDock 以及PyMOL 软件进行分子对接;使用R语言对核心靶点进行基因本体（gene ontology，GO）功能和京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析;采用Cytoscape 3.7.2软件构建桃红四物汤核心靶点-通路网络。结果：经筛选后，得到桃红四物汤有效成分47个及对应靶点237个;PSCI的潜在靶点基因513个;药物-疾病交集靶点50个，核心靶点涉及蛋白激酶B1（protein kinase B1，AKT1）、白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子（tumor necrosis factor，TNF）、白细胞介素-1β（interleukin-1β，IL-1β）、血管内皮生长因子A（vascular endothelial growth factor A，VEGFA）等。分子对接结果显示，槲皮素、β-谷甾醇、山柰酚均与AKT1、IL-6、TNF、IL-1β、VEGFA有较好的亲和力，其中槲皮素与TNF、β-谷甾醇与TNF、山柰酚与VEGFA的结合能最大，具有较强的结合活性。GO功能分析得出2 039个生物过程、44个细胞组分、73个分子功能，KEGG通路分析发现122条相关信号通路，包括糖基化终末产物（advanced glycation end products,AGE）/糖基化终末产物受体（receptor of advanced glycation end products,RAGE）信号通路、血流剪切应力与动脉粥样硬化信号通路、白细胞介素-17（interleukin-17，IL-17）信号通路等。结论：槲皮素、β-谷甾醇及山柰酚等是桃红四物汤防治PSCI的有效成分，其机制可能与AGE-RAGE信号通路、血流剪切应力与动脉粥样硬化信号通路、IL-17信号通路等有关。 |
| 关键词: 卒中后认知障碍 桃红四物汤 网络药理学 分子对接 作用机制 |
| DOI： |
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| Mechanism of action of Taohong Siwu decoction in prevention and treatment of post-stroke cognitive impairment: A study based on network pharmacology and molecular docking |
| GAO Zemeng,FAN Xiangzhen,WANG Ruixue |
| (Department of Rehabilitation Medicine，Binzhou Medical University Hospital，Binzhou 256600，Shandong，China;School of Special Education and Rehabilitation，Binzhou Medical University，Yantai 264003，Shandong，China) |
| Abstract: |
| Objective: To investigate the mechanism of action of Taohong Siwu decoction in the prevention and treatment of post-stroke cognitive impairment (PSCI） based on network pharmacology and molecular docking.Methods: TCMSP database was used to obtain the effective constituents of Taohong Siwu decoction and their corresponding targets，and GeneCards and OMIM databases were used to obtain the targets associated with PSCI.Venny 2.1.0 software was used to obtain the common targets of the drug and the disease，and STRING database was used to establish a protein-protein interaction network and identify potential core targets.AutoDock and PyMOL were used for molecular docking;R language was used to perform the gene ontology (GO） functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG） pathway enrichment analysis of core targets;Cytoscape 3.7.2 was used to construct a core target-pathway network for Taohong Siwu decoction.Results: After screening，a total of 47 effective constituents and 237 corresponding targets were obtained，as well as 513 potential target genes of PSCI and 50 drug-disease intersecting targets，and the core targets included protein kinase B1 (AKT1），interleukin-6 (IL-6），tumor necrosis factor (TNF），interleukin-1β (IL-1β），and vascular endothelial growth factor A (VEGFA）.Molecular docking showed that quercetin，beta-sitosterol，and kaempferol had good affinity with AKT1，IL-6，TNF，IL-1β，and VEGFA，with the highest binding energy between quercetin and TNF，between beta-sitosterol and TNF，and between kaempferol and VEGFA，suggesting a relatively strong binding activity.The GO functional enrichment analysis obtained 2039 biological processes，44 cell components，and 73 molecular functions，and the KEGG pathway enrichment analysis obtained 122 related signaling pathways，including the advanced glycation end products/receptor of advanced glycation end products (AGE/RAGE） signaling pathway，the blood shear stress and atherosclerosis signaling pathway，and the interleukin-17 (IL-17） signaling pathway.Conclusion: Quercetin，beta-sitosterol，and kaempferol are effective constituents in Taohong Siwu decoction for the prevention and treatment of PSCI，and its mechanism might be associated with the AGE-RAGE signaling pathway，the blood shear stress and atherosclerosis signaling pathway，and the IL-17 signaling pathway. |
| Key words: post-stroke cognitive impairment Taohong Siwu decoction network pharmacology molecular docking mechanism of action |
