基于网络药理学探讨补阳还五汤抗脑缺血损伤的分子机制研究
首发时间:2020-02-12
摘要:目的:运用网络药理学和生物信息学方法挖掘补阳还五汤抗脑缺血损伤的分子机制,并进行动物实验验证。方法:通过TCMSP、GEO、Drugbank等数据库挖掘补阳还五汤的活性成分与预测靶点及脑缺血的相关靶点基因,并得到药物-疾病的关键作用基因。通过Cytoscape软件与String数据库构建疾病-靶点-活性成分-药物网络、靶点蛋白互作网络,并得到核心作用基因。对核心作用基因进行基因功能富集分析及基因通路富集分析,探讨补阳还五汤抗脑缺血损伤的分子机制,并进行动物实验验证。结果:共计筛选出补阳还五汤抗脑缺血损伤的25个核心作用靶点,主要涉及到蛋白磷酸化、基因翻译与蛋白合成、炎症反应等生物过程,主要富集在PI3K-Akt、HIF-1、Ras、Rap1、MAPK等信号通路。另外动物实验也证实补阳还五汤调控PI3K-AKT通路的作用。结论:补阳还五汤抗脑缺血损伤具有多成分、多靶点协同作用的特点,能够通过多条信号通路及多个生物学过程发挥抗脑缺血损伤的作用。
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Research on the Molecular Mechanism of Buyang Huanwu Decoction Against Cerebral Ischemia Based on Network Pharmacology
Abstract:OBJECTIVE: To explore the molecular mechanism of Buyang Huanwu Decoction against cerebral ischemic injury using network pharmacology and bioinformatics methods, and to verify it by animal experiments. Methods: TCMSP, GEO, Drugbank and other databases were used to mine the active ingredients of Buyang Huanwu Decoction and target genes related to predictive targets and cerebral ischemia, and to obtain key genes for drug-disease. The Cytoscape software and the String database were used to construct the disease-target-active ingredient-drug network and target protein interaction network, and the core-acting genes were obtained. The gene function enrichment analysis and gene pathway enrichment analysis of core-acting genes were conducted to investigate the molecular mechanism of Buyang Huanwu Decoction against cerebral ischemic injury, and animal experimental verification was performed. Results: A total of 25 core action targets of Buyang Huanwu Decoction against cerebral ischemic injury were screened, which mainly involved biological processes such as protein phosphorylation, gene translation and protein synthesis, and inflammatory response. They were mainly enriched in PI3K-Akt, HIF-1, Ras, Rap1, MAPK and other signal pathways. In addition, animal experiments also confirmed the role of Buyang Huanwu Decoction in regulating the PI3K-AKT pathway. Conclusion: Buyang Huanwu Decoction has the characteristics of multi-component and multi-target synergy against cerebral ischemic injury, and it can exert anti-ischemic injury through multiple signal pathways and multiple biological processes.
Keywords: Buyang Huanwu Decoction Cerebral Ischemia Bioinformatics Network Pharmacology
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基于网络药理学探讨补阳还五汤抗脑缺血损伤的分子机制研究
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