基于GEO数据库结合网络药理学及分子对接技术探讨肉苁蓉防治慢性心力衰竭的分子作用机制  

Exploring the mechanism of action of chronic heart failure curing by Desertliving cistanche based on network pharmacology combined with multi-chip analysis of GEO database

作　　者：叶泽麒 袁崧展 邓少东 肖梦媛 罗梓财 张书琪 龚美盈 陈建英 YE Zeqi;YUAN Songzhan;DENG Shaodong;XIAO Mengyuan;LUO Zicai;ZHANG Shuqi;GONG Meiying;CHEN Jianying(Structural Heart Disease Department,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China)

机构地区：[1]广东医科大学附属医院结构性心脏病专科,湛江524001 [2]广东医科大学第二临床医学院科研平台 [3]广东医科大学附属东莞第一医院国医院

出　　处：《环球中医药》2025年第4期736-750,共15页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81370242);广东医科大学学科建设项目(4SG21229GDGFY01);广东医科大学校级大学生创新创业训练计划项目(GDMU2023036、GDMU2023081);广东医科大学青年科研培育基金(GDMUQ2021011);湛江市科技计划(2022A01183、2022A01166);广东省省级大学生创新创业训练计划(S202310571076);广东医科大学附属医院院内资助类临床研究项目(LCYJ2022B006)。

摘　　要：目的 基于生物信息学及网络药理学分析肉苁蓉防治慢性心力衰竭(chronic heart failure, CHF)的分子作用机制。方法 采用TCMSP、Swiss Target Prediction、ETCM、PharmMapper及检索文献筛选肉苁蓉的有效成分及作用靶标。在Gene Expression Omnibus(GEO)数据库下载GSE16499、GSE42955、GSE84796基因芯片筛选差异基因数据集,整合GeneCard、DisGeNET、DiGSeE、GEO等数据库的数据集得到CHF潜在疾病基因。利用String数据库和Cytoscape 3.7.2软件构建肉苁蓉有效成分—靶标可视化网络,通过拓扑学参数分析获取核心靶标。利用DVAID数据库进行GO和KEGG通路富集分析,构建肉苁蓉有效成分—靶标—通路网络。最后采用Autodock软件可视化展示核心靶标与有效成分进行分子对接的验证结果。结果 筛选得到肉苁蓉有效成分55个,潜在靶标630个,包括红景天苷、胃动素、蝙蝠葛碱等关键成分以及甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-hosphate dehydrogenasem, GAPDH)、白细胞介素6(interleukin 6,IL-6)、肿瘤坏死因子(tumor necrosis factor, TNF)等核心靶标,关键通路主要涉及磷脂酰肌醇-3-激酶(phosphoinositide-3-kinase, PI3K)-蛋白激酶B(protein kinase B,Akt)信号通路、癌症中心碳代谢、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)信号通路等,分子对接结果表明关键成分和核心靶标结合较好。结论 多成分、多靶标、多通路探讨了肉苁蓉防治CHF的分子作用机制,提示肉苁蓉的有效成分可能作用于CHF的多个靶标、通路从而改善心衰症状,可为肉苁蓉的临床应用及进一步的实验验证提供理论依据。Objective To analyse the molecular mechanism of action of Desertliving cistanche against chronic heart failure(CHF)using bioinformatics and network pharmacology.Methods The database of TCMSP,Swiss Target Prediction,ETCM,PharmMapper and literature search were used to screen the compounds and targets of Desertliving cistanche.The Gene Expression Omnibus(GEO)database was used to download the GSE16499,GSE42955,GSE84796 gene chips to screen the differential gene datasets,and the datasets from GeneCard,DisGeNET,DiGSeE,GEO and other databases were integrated to obtain the potential disease genes of CHF.The String database and Cytoscape 3.7.2 software were used to construct the active ingredient of Desertliving cistanche-target visualisation network,and the core targets were obtained by topological parameter analysis.The GO and KEGG pathway enrichment analyses were performed using the DVAID database to construct the active ingredient of Desertliving cistanche-target-pathway network.Finally,Autodock software was used to visualise the results of molecular docking between core targets and compounds.Results 55 compounds and 630 potential targets of Desertliving cistanche were screened,including key components such as slidroside,motilin,dauricine,and core targets such as glyceraldehyde-3-hosphate dehydrogenasem(GAPDH),interleukin 6(IL-6),tumor necrosis factor(TNF),etc.The key pathways were mainly related to the phosphoinositide-3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,central carbon metabolism in cancer,and the PI3K-Akt signaling pathway and central carbon metabolism in cancer.The key pathways mainly involved PI3K-Akt signaling pathway,central carbon metabolism in cancer,mitogen-activated protein kinase(MAPK)signaling pathway,etc.The molecular docking results showed that the key components and core targets were well combined.Conclusion A multi-component,multi-target and multi-pathway study were conducted to investigate the molecular mechanism of Desertliving cistanche against CHF.The result suggested that the act

关 键 词：肉苁蓉 慢性心力衰竭 网络药理学 生物信息学 GEO数据库 分子对接 核心靶标 

分 类 号：R285[医药卫生—中药学]