基于生物信息学、网络药理学和分子对接方法探讨苦丁茶治疗扩张型心肌病的作用机制  

Mechanism of Ilex Kudingcha for the treatment of dilated cardiomyopathy based on bioinformatics,network pharmacology and molecular docking methods:an exploration study

作　　者：黎承班 高书亚 何斌 权里平 王育博 余林星 刘顺利 刘莉 LI Chengban;GAO Shuya;HE Bin;QUAN Liping;WANG Yubo;YU Linxing;LIU Shunli;LIU Li(Graduate School,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;Department of Cardiovascular Medicine,Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China)

机构地区：[1]右江民族医学院研究生学院,广西百色市533000 [2]右江民族医学院附属医院心血管内科,广西百色市533000

出　　处：《广西医学》2024年第11期1716-1726,共11页Guangxi Medical Journal

基　　金：国家自然科学基金(82360080);广西自然科学基金(2023GXNSFAA026010)。

摘　　要：目的基于生物信息学、网络药理学和分子对接方法探讨苦丁茶治疗扩张型心肌病(DCM)的作用机制。方法通过中药系统药理学数据库与分析平台、PubChem、SwissTargetPrediction、UniProt等数据库筛选苦丁茶的活性化学成分及其作用靶点。通过GeneCards®数据库、OMIM®数据库和DisGeNET数据库获取DCM相关靶点。将上述靶点取交集,采用STRING数据库和Cytoscape软件构建交集靶点的蛋白⁃蛋白相互作用(PPI)网络,筛选核心靶点。利用Cytoscape软件构建成分⁃靶点网络图,筛选关键活性成分。通过R语言软件对交集靶点进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。利用GEO数据库的在线工具GEO_(2)R分别对3个微阵列数据集GSE1145、GSE42955和GSE5406进行分析,筛选差异表达基因,针对差异表达基因与核心靶点基因中的共有基因,通过R语言软件绘制受试者工作特征(ROC)曲线分析其预测效能。针对关键活性成分及核心靶点进行分子对接验证。结果共筛选出苦丁茶活性化学成分9个及其作用靶点369个,DCM相关靶点1597个,两者交集靶点105个。苦丁茶治疗DCM的关键活性成分包括槲皮素、山柰酚、β⁃谷甾醇、坡模酸等,核心靶点包括丝氨酸/苏氨酸激酶1(AKT1)、原癌基因酪氨酸蛋白激酶(SRC)、肿瘤坏死因子(TNF)、Jun原癌基因,AP⁃1转录因子亚基(JUN)等。交集靶点涉及伤口愈合、上皮细胞增殖、生殖系统发育、对氧化应激的反应等生物过程,膜微域膜筏、膜筏、质膜的外侧、黏着斑等细胞组分,信号受体激活剂活性、受体配体活性、蛋白丝氨酸/苏氨酸/酪氨酸激酶活性及细胞因子受体结合等分子功能,以及脂质和动脉粥样硬化、PI3K/AKT信号通路、AGE/RAGE信号通路等信号通路。AKT1、SRC、TNF、HSP90AA1和JUN在GSE1145、GSE42955、GSE55406三个GEO数据集中存在差异表达,且诊断DCM的效能较Objective To investigate the mechanism of Ilex Kudingcha for the treatment of dilated cardiomyopathy(DCM)based on bioinformatics,network pharmacology,and molecular docking methods.Methods Active chemical components and their effect targets of Ilex Kudingcha were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the databases such as PubChem,SwissTargetPrediction,and UniProt.Targets related to DCM were obtained from the databases of GeneCards®,OMIM®,and DisGeNET,and the intersection of the aforementioned targets was acquired.The protein⁃protein interaction(PPI)network of the intersection targets was established for screening the core targets by using the STRING database and Cytoscape software.The components⁃targets network diagram was established for screening the key active components by employing the Cytoscape software.Through the R language software,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection targets.The online tool GEO_(2)R of GEO database was used to perform analysis on 3 microarray datasets of GSE1145,GSE42955,and GSE5406 for screening differentially expressed genes.For common genes between differentially expressed genes and core target genes,the receiver operating characteristic(ROC)curve was drawn by the R language software to analyze their predictive efficiency.Molecular docking validation was performed on the key active components and core targets.Results A total of 9 active chemical components and 369 effect targets of Ilex Kudingcha were screened.Targets related to DCM were 1597,and the intersection targets were 105.The key active components of Ilex Kudingcha for treating DCM contained quercetin,kaempferol,β⁃sitosterol,and pomolic acid,etc.,and the core targets included serine/threonine kinase 1(AKT1),proto⁃oncogene tyrosine protein kinase(SRC),tumor necrosis factor(TNF),Jun proto⁃oncogene,AP⁃1 transcription factor subunit(JU

关 键 词：扩张型心肌病 苦丁茶 生物信息学 网络药理学 分子对接 作用机制 

分 类 号：R542.2[医药卫生—心血管疾病]