基于网络药理学探讨血府逐瘀汤治疗颅脑损伤作用机制

Study on the Mechanism of Xuefu Zhuyu Decoction in the Treatment of Traumatic Brain Injury Based on Network Pharmacology

目的:利用网络药理学与分子对接技术研究血府逐瘀汤治疗颅脑损伤的有效成分和作用机制。方法:从TCMSP数据库中筛选出血府逐瘀汤的活性成分及药物靶点,用Genecards、OMIM和DisGeNET数据库预测颅脑损伤的疾病靶点,取药物靶点和疾病靶点的交集作为潜在靶点,并在STRING数据库中获得靶点蛋白质互作网络,导入Cytoscape软件获得关键靶点和有效成分,在David数据库中进行关键靶点的GO和KEGG富集分析,最后用Autodock vina软件进行有效成分和关键靶点的分子对接验证。结果:共筛选得到血府逐瘀汤治疗颅脑损伤11种有效成分和10个关键靶点,通过分子对接验证了刺芒柄花素、异鼠李素、杨梅酮、柚皮素、β-谷甾醇等有效成分和ESR1、JUN、HSP90AA1、MAPK14等关键靶点之间的相互作用力和分子间结合力很强。富集分析结果表明有效成分和关键靶点通过参与调节NOD样受体信号通路、VEGF信号通路、Toll样受体信号通路和TNF信号通路而发挥治疗TBI的作用。结论:血府逐瘀汤治疗颅脑损伤的作用机制与炎症反应、血管新生、NO合成以及细胞凋亡等生物过程有关。

Objective:To research the pharmacodynamic components and mechanism of Xuefu Zhuyu De⁃coction in the treatment of traumatic brain injury(TBI)by network pharmacology and molecular docking technology.Methods:TCMSP database was used to acquire the active components and related drug targets of Xuefu Zhuyu Decoction,and Genecards,OMIM and DisGeNET databases were predicte the disease targets of TBI.As the potential targets which was the intersection of drug targets and disease targets,its protein interaction network was obtained in the STRING database,and key targets and pharmacodynamic components were analysed by Cytoscape software.Futhermore,David database carried out the GO and KEGG enrichment analysis of key targets.Eventually,Autodock vina software determined the molecular docking verification of active ingredients and key targets.Results:The study totally discovered 11 pharma⁃codynamic components and 10 potential targets of Xuefu Zhuyu Decoction in the treatment of TBI.Through molecular docking verification,it was proved that the interaction and intermolecular binding force between the significant pharmacodynamic components such as formononetin,isorhamnetin,myrica⁃none,naringenin,β-sitosterol and the key targets such as ESR1,JUN,HSP90AA1,MAPK14 were very strong.The results of bioinformatics analysis showed that these pharmacodynamic components and key targets were involved in the regulation of NOD-like receptor signal pathway,VEGF signal pathway,Toll-like receptor signaling pathway and TNF signaling pathway and played a role in the treatment of TBI.Conclusion:The mechanism of TBI treatment was related to the biological processes such as inflammation reaction,angiogenesis,NO biosynthetic,and cell apoptosis.