摘要
目的:基于网络药理学及分子对接方法探讨丹参有效成分治疗冠心病和脑卒中"异病同治"的作用机制及关键靶点.方法:通过中药系统药理学数据库和分析平台(TCMSP)、在线人类孟德尔遗传数据库(OMIM)、DrugBank等数据库筛选丹参治疗冠心病及脑卒中的潜在靶点,并通过 Metascape在线平台进行靶点蛋白-蛋白相互作用(PPI)、基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析,使用Cytoscape3.9.1构建活性成分-关键靶点-核心通路网络,筛选出核心成分.采用分子对接模拟核心成分与关键靶点的结合程度.结果:筛选丹参治疗冠心病与脑卒中"异病同治"的潜在靶点52个,主要富集于糖基化终末产物/糖基化终末产物受体(AGE/RAGE)、血小板激活、脂质与动脉粥样硬化、流体剪应力与动脉粥样硬化等通路.核心药效成分与磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)、一氧化氮合酶(NOS3,eNOS)、B淋巴细胞瘤相关蛋白-2(Bcl-2)、环氧合酶2(PTGS2)、整合素亚基α2b(ITGA2B)、基质金属蛋白酶9(MMP9)等靶点结合稳定.结论:丹参"异病同治"冠心病与脑卒中主要通过抗血小板活化与聚集、保护心脑血管细胞、稳定斑块、减轻炎症等机制改善动脉粥样硬化,并存在靶点竞争及协同疗效的潜在可能.
Abstract
Objective:To explore the heteropathy mechanism and key therapeutic targets of the"same treatment for different diseases"of salvia miltiorrhiza for the treatment of coronary heart disease(CHD)and stroke by network pharmacology and molecular docking.Methods:Potential targets for the treatment of coronary heart disease and stroke were screened through traditional Chinese medicine(TCM)System Pharmacology Database and Analysis Platform(TCMSP),online human Mendelian Genetic database(OMIM),DrugBank,and other databases.Target protein-protein interaction(PPI),Gene ontology(GO)and Kyoto Genome Encyclopedia(KEGG)pathway analysis via the Metascape online platform.The active ingredient-key target-core pathway network was constructed using Cytoscape 3.9.1 to screen out the core components.Molecular docking was used to simulate the degree of binding between core components and key targets.Results:Fifty-two potential targets of salvia miltiorrhea for the treatment of coronary heart disease and stroke were selected,mainly concentrated in the pathways of advanced glycation end products(AGE)/receptor for advanced glycation end products(RAGE),platelet activation,lipid and atherosclerosis,fluid shear stress and atherosclerosis.The core pharmacodynamic components stably bound to phosphatidylinositol-3-kinase(PI3K),protein kinase B(AKT),nitric oxide synthase(NOS3,eNOS),B lymphocytoma-associated protein-2(Bcl-2),cyclooxygenase 2(PTGS2),integrin subunit α2b(ITGA2B),matrix metalloproteinase 9(MMP9),and other targets.Conclusion:The"same treatment for different diseases"of salvia miltiorrhoea can improve atherosclerosis in coronary heart disease and stroke mainly through anti-platelet activation and aggregation,protection of cardiovascular and cerebrovascular cells,stabilization of plaque,and reduction of inflammation,with potential target competition and synergistic effects.
基金项目
中国中医科学院科技创新工程项目(CI2021A04703)
中国中医科学院优秀青年科技人才培养专项(ZZ15-YQ-019)
万方数据