基于网络药理学探讨加味柴胡...心病伴焦虑_抑郁的作用机制_吴戈.pdf

论著生物信息技术基金项目:国家自然科学基金(82060835);广西自然科学基金(2022GXNSFDA035086)第一作者简介:吴戈，硕士，住院医师，研究方向:方剂配伍规律的临床及基础。通信作者简介:孔鹏云，硕士，讲师，研究方向:方剂配伍规律的临床及基础。通信作者简介:杨力强，博士，教授，研究方向:方剂配伍规律的临床及基础。基于网络药理学探讨加味柴胡疏肝散治疗冠心病伴焦虑/抑郁的作用机制吴戈陆雅席杨苹孔鹏云杨力强(广西中医药大学基础医学院，广西南宁市530200)【摘要】目的运用网络药理学方法，探讨加味柴胡疏肝散治疗冠心病伴焦虑/抑郁的作用机制。方法运用中药系统药理学数据库与分析平台获取加味柴胡疏肝散所含中药的有效活性成分及其作用靶点。通过 GeneCards、OMIM、TTD 数据库筛选冠心病及焦虑/抑郁的相关靶点，并对两类疾病相关靶点取交集。对有效活性成分的作用靶点与疾病相关靶点进行交集，获得交集靶点作为加味柴胡疏肝散治疗冠心病伴焦虑/抑郁的潜在作用靶点。使用 CytoScape 3 8 0 软件构建药物成分-疾病-靶点网络图。利用 STING 数据库构建交集靶点的蛋白-蛋白相互作用(PPI)网络，并筛选加味柴胡疏肝散治疗冠心病伴焦虑/抑郁的核心靶点(度值30)。使用 Metascape 数据库对交集靶点进行基因本体论(GO)功能富集分析及京都基因和基因组百科全书(KEGG)通路富集分析。结果(1)共获得有效活性成分 233 个，有效活性成分的作用靶点 161 个，交集靶点 106 个。(2)药物成分-疾病-靶点网络的节点度值较高的前 15 个有效活性成分中，黄酮类成分共有 7个，包括槲皮素、山柰酚、木犀草素、川陈皮素、柚皮素、美迪紫檀素、异鼠李素。(3)PPI 网络中，度值30 的靶点有 26 个，其中前 10 个靶点为 TNF、IL-6、IL-1、VEGFA、TP53、JUN、EGF、PTGS2、MAPK3、ES1。(4)GO 功能富集分析结果显示，交集靶点主要富集在细胞对氮化合物的反应、循环系统过程、内分泌调控等生物过程，膜筏、受体复合物、突触后膜、囊腔等细胞组分，以及 G 蛋白偶联胺受体活性、儿茶酚胺结合、氧化还原酶活性、核受体活性等分子功能。KEGG 通路富集分析结果显示，交集靶点主要富集在神经活性配体-受体相互作用信号通路、流体剪切应力与动脉粥样硬化通路、钙离子信号通路、PI3K/AKT 信号通路等。结论加味柴胡疏肝散治疗冠心病伴焦虑/抑郁的作用机制可能与抑制炎症反应、调控细胞凋亡和血管生成有关。【关键词】冠心病;焦虑;抑郁;双心疾病;加味柴胡疏肝散;作用机制;网络药理学【中图分类号】541 4【文献标识码】A【文章编号】0253-4304(2023)03-0309-08DOI:10 11675/j issn 0253-4304 2023 03 11Mechanism of modified Chaihu Shugan Powder for the treatment of coronary heart disease andconcomitant anxiety/depression:an exploration based on network pharmacologyWU Ge，LU Yaxi，YANG Ping，KONG Pengyun，YANG Liqiang(School of Basic Medicine，Guangxi University of Chinese Medicine，Nanning 530200，Guangxi，China)【Abstract】ObjectiveTo explore the mechanism of modified Chaihu Shugan Powder for the treatment of coronaryheart disease and concomitant anxiety/depression by employing network pharmacology method MethodsThe effectivelyactive components of Traditional Chinese Medicines contained in modified Chaihu Shugan Powder and their effect targetswere acquired by employing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Thetargets related to coronary heart disease and concomitant anxiety/depression were screened from the databases of GeneCards，OMIM，and TTD，and the intersection was performed on targets related to the two diseases The intersection wasperformed on effect targets of effectively active components and disease-related targets，and the obtained intersectiontargets were taken as potential effect targets of modified Chaihu Shugan Powder for the treatment of coronary heartdisease and concomitant anxiety/depression The network chart of drug component-disease-target was constructed bythe CytoScape 3 8 0 software The protein-protein interaction(PPI)network of intersection targets was constructed903广西医学2023 年 2 月第 45 卷第 3 期by the STING database，and the core targets(degree value30)of modified Chaihu Shugan Powder for the treatmentof coronary heart disease and concomitant anxiety/depression were screened The Gene Oncology(GO)functionalenrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis wereperformed on intersection targets by the Metascape database esults(1)A total of 233 effectively active components，161 effect targets of effectively active components，and 106 intersection targets were obtained(2)Among the top 15effectively active components with high node degree value in the drug component-disease-target network，there were 7flavonoids components，including quercetin，kaempferol，luteolin，nobiletin，naringenin，medicarpin，and isorhamnetin(3)Among PPI network，there were 26 targets with degree value30，among which the top 10 targets were TNF，IL-6，IL-1，VEGFA，TP53，JUN，EGF，PTGS2，MAPK3，and ES1(4)The results of GO functional enrichmentanalysis revealed that intersection targets were mainly enriched in biological processes with respect to cellular responsesto nitrogen compounds，circulatory system processes，endocrine regulation，etc，and cellular compositions of membraneraft，receptor compound，postsynaptic membrane，and allantoic cavity，etc，as well as molecular function in terms ofG protein coupled amine receptor activity，catecholamine binding，oxidoreductase activity，and nuclear receptor activity，etc The results of KEGG pathway enrichment analysis revealed that the intersection targets were mainly enriched inneuroactive ligand-receptor interaction signaling pathway，fluid shear stress and atherosclerotic pathways，calcium ionsignaling pathway，and PI3K/AKT signaling pathway，etc ConclusionThe mechanism of modified Chaihu ShuganPowder for the treatment of coronary heart disease and concomitant anxiety/depression may be related to inflammatoryresponse inhibition，cell apoptosis regulation，and angiogenesis【Key words】Coronary heart disease，Anxiety，Depression，Bicardiac disease，Modified Chaihu ShuganPowder，Mechanism，Network Pharmacology冠心病是目前公认的身心疾病。在冠心病的发生发展过程中，社会外部环境、患者的心理压力等会对其产生重要的影响1。有研究报告，精神刺激可促进心脑血管疾病的发生和发展，因此会对患者的生命、生存质量及心理健康等产生重大影响2。在冠心病患者中，有 18%60%的患者存在不同程度的抑郁，28%70%的患者存在忧虑症状，冠心病伴发焦虑/抑郁的概率约为 14 3%3 4。因心血管疾病与心理障碍疾病具有密切的相关性，所以临床上常称伴随着心理疾病的心血管疾病为“双心疾病”。柴胡疏肝散是临床上治疗焦虑、抑郁的常用复方，具有疏肝解郁、行