塞络通治疗脑缺血的网络药理与分子对接技术研究

Research on the Anti-cerebral Ischemic Mechanism of Sailuotong Based on Network Pharmacology and Molecular Docking Technology

目的通过网络药理学及分子对接技术探究中药复方塞络通治疗脑缺血疾病的潜在物质基础和分子机制。方法本团队前期研究证实了塞络通中的17种活性成分,以此为基础进行后续研究。通过TCMSP、SwissTargetPrediction、PharmMapper、GeneCard数据库预测活性成分的作用靶点,结合OMIM、DisGeNET数据库获得脑缺血的对应基因靶点,两者取交集后使用String数据库及Cytoscape软件构建蛋白互作网络(PPI),并分析得出Degree值排名靠前的作用靶点。采用Metascape工具对塞络通治疗脑缺血的交集靶点进行GO功能富集分析和KEGG通路富集分析,最后运用AutoDockTools软件进行分子对接验证。结果塞络通复方活性化合物-脑缺血疾病靶点网络包含301个靶点,关键靶点涉及Akt1、SRC、ESR1、GSK3B、EGFR等,靶点基因功能偏向物质代谢、蛋白质丝氨酸/苏氨酸蛋白激酶活性、突触形成、炎症反应等。分子对接结果表明塞络通中主要活性成分与关键靶点均有一定结合能力。结论塞络通可能通过调节物质代谢参与脑缺血后的神经保护作用。

Objective:To explore the potential material basis and molecular mechanism of traditional Chinese medicine compound Sailuotong in the treatment of cerebral ischemic disease through network pharmacology and molecular docking technology.Methods:The active ingredients in the traditional Chinese medicine compound Sailuotong were obtained through literature,and the target of action of the active ingredients was predicted using TCMSP,SwissTargetPrediction,PharmMapper,and GeneCard databases.The corresponding gene targets for cere⁃bral ischemia were obtained by combining OMIM and DisGeNET databases.After the intersection of the two,a pro⁃tein interaction network(PPI)was constructed using String database and Cytoscape software,and analyzed to deter⁃mine the target of action with the highest Degree value ranking.Metascape tool was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the intersection targets of Sailuotong in the treat⁃ment of cerebral ischemia.Finally,molecular docking validation was performed using AutoDockTools software.Re⁃sults:The Sailuotong compound active compound target network for cerebral ischemic disease contained 301 tar⁃gets,with key targets involving Akt1,SRC,ESR1,GSK3B,EGFR,etc.The target gene function was biased towards substance metabolism,protein serine/threonine protein kinase activity,synaptic formation,inflammatory response,etc.The molecular docking results indicated that the main active ingredients in Sailuotong had a certain binding ability to key targets.Conclusion:Sailuotong may participate in neuroprotective effects after cerebral ischemia by regulating substance metabolism.