基于分子对接和网络药理学的参附注射液干预深静脉血栓的机制探析

Study on the mechanism of Shenfu injection in intervention of deep vein thrombosis based on network pharmacology and molecular docking

目的利用网络药理学研究方法和分子对接技术预测参附注射液干预深静脉血栓形成的作用机制。方法利用CNKI数据库进行文献检索,挖掘参附注射液主要有效成分,利用SIB数据库预测有效成分作用靶点,通过GeneCards、DisGeNET等数据库筛选出深静脉血栓形成的相关靶标,进而得到参附注射液治疗深静脉血栓的潜在靶点。通过STRING数据库分析潜在治疗靶点蛋白相互作用网络并筛选关键靶点,与利用Cytoscape软件构建的“成分-靶标”网络中的核心有效成分进行分子对接。利用Cluego和David6.8v数据库分别对药物和疾病的潜在治疗靶点进行GO分析和KEGG富集通路分析。结果来自参附注射液中红参和附片中22个有效成分通过干预114个靶点、85条通路发挥干预深静脉血栓形成的作用。AKT1、VEGFA、HSP90AA1、MAPK1、PIK3CA等可能是参附注射液治疗深静脉血栓形成的关键靶点。结论参附注射液有效成分可能通过抑制血管壁细胞炎性反应、抗氧化应激、调节血管稳态等药理作用治疗深静脉血栓形成。

Objective To explore the mechanism of Shenfu injection(SFI)in intervention on deep vein thrombosis(DVT)based on network pharmacology combined with molecular docking.Methods The targets of DVT were screened out by retrieving GeneCards,DisGeNet and other databases.The effective components of each traditional Chinese medicine in SFI were obtained through literature review and their targets were predicted based on SIB database.Cytoscape software was used to construct the component-target network.The protein-protein interaction(PPI)network and the key targets were constructed by STRING database,and the interaction between core ingredients and key targets was verified by using Autodock vina software.The analyses of GO function and KEGG pathway enrichment of the key targets were performed with Cluego and DAVID6.8v database,respectively.Results The study showed that 22 components from Hongshen and Fupian could be used to treat DVT involving 114 gene targets and 85 signaling pathways.Through Maestro software,top four proteins were found to bind well to core ingredients.AKT1,VEGFA,HSP90AA1,MAPK1,and PIK3CA were proposed to be the key targets for the treatment of deep vein thrombosis with Shenfu injection.Conclusion The effective components of SFI may treat DVT by inhibiting the inflammatory reaction of blood vessel wall and oxidative stress,maintaining homeostasis of vascular system and other pharmacological actions.