基于网络药理学的土鳖虫破血逐瘀作用机制研究  

Soudy on Mechanism of Blood-breaking and Stasis-removing Effects of Eupolyphaga Steleophaga Based on Network Pharmacology

作　　者：王少平 赵一慕 李盼盼 宋书祎 韩菲 张加余 代龙 WANG Shao-ping;ZHAO Yi-mu;LI Pan-pan;SONG Shu-yi;HAN Fei;ZHANG Jia-yu;DAI Long(Binzhou Medical University,Yantai 264003,China)

机构地区：[1]滨州医学院,山东烟台264003

出　　处：《中国现代中药》2021年第3期457-463,469,共8页Modern Chinese Medicine

基　　金：滨州医学院科研启动项目(BY2018KYQD11);中央本级重大增减支项目(2060302-1907-08);山东省中药资源普查项目(2019-1020)。

摘　　要：目的:基于网络药理学分析土鳖虫对破血逐瘀相关疾病的作用机制。方法:经文献查阅并结合PubChem、SwissADME、SwissTargetPrediction和TCMSP等数据库对土鳖虫已知成分及其对应靶点进行搜集,并与经GeneCards、OMIM、TTD、HPO数据库搜索得到的“破血逐瘀”相关靶点进行交互分析得到共同靶点;通过蛋白-蛋白质-蛋白质相互作用(PPI)分析、基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,构建土鳖虫“成分-靶点-疾病”网络,探讨土鳖虫破血逐瘀功效的作用机制。同时采用体外纤溶实验评价土鳖虫水溶性蛋白质与其他成分的活性差异。结果:筛选得到土鳖虫活性化合物54个,共对应靶点653个;与血瘀相关的17种疾病的16141个作用靶点经交互分析得出两者共有靶点26个。GO和KEGG分析结果表明,土鳖虫已知成分主要涉及嘌呤代谢通路、细胞能量代谢通路、环磷酸鸟苷(cGMP)信号通路、Toll样受体信号通路、醛固酮合成代谢通路、三酰甘油合成通路等13条信号通路,通过干预DNA转录、细胞能量代谢等生物功能发挥药效。同时体外纤溶实验得出土鳖虫水溶性蛋白质较其他成分表现出更强的纤溶活性。结论:土鳖虫已知活性成分并不能很好的证明其对破血逐瘀相关疾病的治疗有显著的效果。结合土鳖虫水溶性蛋白质促纤溶作用,为下一步土鳖虫纤溶物质基础的研究提供参考。Objective:To explore the mechanism of Eupolyphaga Steleophaga in the treatment of blood stasis related diseases based on network pharmacology.Methods:The known components and corresponding targets of Eupolyphaga Steleophaga were collected by the related database(PubChem,SwissADME,SwissTargetPrediction and TCMSP).The relevant targets of″breaking blood and stasis″were searched by professional database(GeneCards,OMIM,TTD and HPO),and the final targets also were obtained compare with the first two parts.Protein-protein interaction(PPI)analysis,gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis were used to predict effects.The difference in fibrinolytic activity between the water-soluble protein and other components was measured using an in vitro model.Results:54 active compounds which correspond to 653 related targets were screened out based on the oral bioavailability(OB)>30%and drug likeness(DL)>0.18 toward the literature databases,and finally 26 targets are obtained through interaction analysis.The results of GO and KEGG analysis showed that the known components of Eupolyphaga Steleophaga were mainly related to 13 signal pathways interfere with biological functions such as DNA transcription and cell energy metabolism.Such as purine metabolism pathway,cell energy metabolism pathway,cyclic guanosinc monphosphate(cGMP)signal pathway,Toll-like receptor signal pathway,aldosterone anabolic pathway,triacylglycerol pathway and so on.Simultaneously,the result of fibrinolysis experiments in vitro showed that the water-soluble protein of Eupolyphaga Steleophaga had strong activity.Conclusion:The present study found that the known active ingredients of Eupolyphaga Steleophaga can not prove that it has a significant effect on the treatment of blood stasis related diseases.However,the composition of woodlouse insect protein was not considered in the analysis,which provided a direction for the next research on the effective components of Eupolyphaga Steleophaga.

关 键 词：土鳖虫 网络药理学 破血逐瘀 心血管疾病 靶点 纤溶 

分 类 号：R285.5[医药卫生—中药学]