基于整合药理学平台探究三棱抗血栓形成及抗血小板聚集的分子机制

Molecular Mechanism of Anti-thrombosis and Anti-platelet Aggregation of Sparganii Rhizoma Based on Integrated Pharmacological Platform

目的:探讨三棱抗血小板聚集及抗血栓形成的分子机制。方法:利用中药整合药理学平台(TCM-IP)的中药材数据库、中药成分数据库和疾病靶标数据库的数据信息和分析功能,检索三棱所含的化学成分信息,构建三棱作用的潜在靶标和疾病靶标之间的相互作用网络,然后富集计算核心靶标,进行基因功能分析和通路分析,再进一步构建"中药材-化学成分-核心靶标-关键通路"多维关系网络。结果:对三棱预测活性成分主要包括黄酮、酚酸等成分,如山柰酚、三棱酸等;抗血栓形成涉及202个核心靶标,包括蛋白激酶Cδ(PRKCD),葡萄糖激酶(GCK),腺嘌呤核糖核苷酸活化蛋白激酶α-2催化亚基等;涉及内分泌系统、循环系统、神经退行性疾病等相关生物过程和信号通路。抗血小板聚集涉及136个核心靶标,包括PRKCD,细胞色素C氧化酶蛋白7C(COX7C),GCK等;涉及帕金森病、循环系统、神经退行性疾病等相关生物过程和信号通路。结论:三棱主要通过调控中枢神经系统的神经递质活性达到调节血管内皮细胞黏附分子表达以及血小板线粒体功能介导血小板的凋亡,从而发挥抗血栓形成及抗血小板聚集的药效作用。

Objective: To study on the molecular mechanism of anti-platelet aggregation and antithrombosis of Sparganii Rhizoma. Method: Based on the data information and analysis functions of traditional Chinese medicine(TCM) database, TCM composition database and target database in TCM platform for integration of pharmacology,information of chemical compositions in Sparganii Rhizoma was retrieved,interaction network between potential targets of Sparganii Rhizoma and disease targets was built,and the key targets were enriched and calculated,the gene functions and pathways were analyzed,multidimensional relationship network of ' herbal medicines-chemical components-key targets-key pathways ' was built. Result: Active ingredients of Sparganii Rhizoma mainly included flavonoids and phenolic acids,such as mountain kaempferol,sanleng acid,linoleic acid,etc. Anti-thrombosis involved 202 key targets,including protein kinase Cδ(PRKCD),glucose kinase(GCK),(PRKAA2),adenosine ribonucleotide activated protein kinase α-2 catalytic subunit,etc;and it was related to the endocrine system,circulatory system,neurodegenerative diseases and other related biological processes and signal pathways. Anti-platelet aggregation involved 136 key targets,including PRKCD,cytochrome C oxidase protein 7 C(COX7 C),GCK,etc;and it was involved in Parkinson’s disease,circulatory system,neurodegenerative diseases and other related biological processes and signal pathways. Conclusion: Sparganii Rhizoma regulates vascular endothelial cell adhesion molecule expression and platelet mitochondrial function mediated apoptosis of platelets mainly through regulating neurotransmitter activity in the central nervous system,in order to exert antithrombotic effect and anti-platelet aggregation effect.