基于GEO 芯片联合网络药理学探讨化瘀通络汤治疗缺血性脑卒中作用机制
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R743

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中山市社会公益与基础研究项目(2021B1065);广东省中医药局资助项目(20191360)


Discussion on Mechanism of Huayu Tongluo Tang in Treating Ischemic Stroke Based on GEO Chip Combined with Network Pharmacology
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    摘要:

    目的:基于GEO 芯片联合网络药理学探讨化瘀通络汤治疗缺血性脑卒中(IS) 的作用机制。方法:通过GEO 芯片结合GeneCards 数据库获取IS 的疾病靶点,利用TCMSP、文献检索结合SwissTargetPrediction 筛选出化瘀通络汤治疗IS 的有效成分和作用靶点,通过STRING 数据库与Cytoscape 3.8.2 软件构建蛋白质相互作用(PPI) 网络及拓扑分析,采用DAVID 数据库和R 语言对共同靶点进行GO 功能及KEGG 通路富集分析,并对化瘀通络汤的主要成分与关键治疗靶点进行分子对接验证。结果:共筛选出疾病靶点3 964 个,化瘀通络汤作用靶点565 个,化瘀通络汤治疗IS 的关键靶点有非受体酪氨酸激酶(Src)、丝裂原活化蛋白激酶3(MAPK3)、表皮生长因子受体(EGFR) 等;富集分析主要涉及神经活性配体-受体相互作用通路、癌症通路、缺氧诱导因子-1 信号通路、丝裂原活化蛋白激酶信号通路等。分子对接结果显示,化瘀通络汤主要活性化合物(木犀草素、槲皮素) 与主要治疗靶点(Src、EGFR) 有较高的结合效能。结论:化瘀通络汤可能通过作用于Src、EGFR 等核心靶点,减轻神经炎症反应、促进血管新生等多个方面发挥治疗IS 的作用。

    Abstract:

    Abstract:Objective:To discuss the mechanism of Huayu Tongluo Tang in treating ischemic stroke(IS) based on GEO chip combined with network pharmacology. Methods: The targets of IS was obtained by GEO chip combined with GeneCards database,effective components and targets of Huayu Tongluo Tang in treating IS were screened by TCMSP and literature retrieval combined with SwissTargetPrediction, the protein- protein interaction(PPI) network and topology analysis were constructed by STRING database and Cytoscape 3.8.2 software,GO function and KEGG pathway enrichment of common targets were analyzed by DAVID database and R language, and molecular docking verification was performed on the main components and key therapeutic targets of Huayu Tongluo Tang. Results:A total of 3 964 targets of the disease and 565 targets of Huayu Tongluo Tang were screened out,and the key targets of Huayu Tongluo Tang treating IS included non-receptor tyrosine kinase(Src),mitogen-activated protein kinase 3(MAPK3), epidermal growth factor receptor(EGFR);enrichment analysis mainly involved neuroactive ligand-receptor interaction pathway,cancer pathway,hypoxia inducible factor-1 signaling pathway and mitogen activated protein kinase signaling pathway. Molecular docking results showed that the main active compounds of Huayu Tongluo Tang, including luteolin and quercetin, had high binding efficiency with the main therapeutic targets,including Src and EGFR. Conclusion:Huayu Tongluo Tang plays a role in the treatment of IS by many aspects,including acting on Src,EGFR and other core targets,reducing neuroinflammation, and promoting angiogenesis.

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王小军,彭慧渊,汪峰,许航敏.基于GEO 芯片联合网络药理学探讨化瘀通络汤治疗缺血性脑卒中作用机制[J].新中医,2022,54(21):13-19

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  • 在线发布日期: 2022-11-15
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