西南乌头治疗心力衰竭的主要活性成分和核心靶基因筛选及其机制分析  

Screening of main active ingredients and core target genes of Aconitum episcopale Leveille for the treatment of heart failure and the mechanism of action

作　　者：李剑 李永国 张云塔 杨用成 夏从龙 LI Jian;LI Yongguo;ZHANG Yunta;YANG Yongcheng;XIA Conglong(College of Pharmacy,Dali University,Dali 671000,China;不详)

机构地区：[1]大理大学药学院,云南大理671000 [2]云南省高等学校云南道地药材资源开发重点实验室,云南大理671000

出　　处：《山东医药》2025年第4期26-31,共6页Shandong Medical Journal

基　　金：云南省李剑专家工作站项目(202005AF150013);云南省大理白族自治州科技计划重大项目(D2019NA03)。

摘　　要：目的筛选西南乌头治疗心力衰竭的主要活性成分及核心靶基因并分析其机制,为心力衰竭的治疗及候选药物开发提供新思路。方法通过检索GenBank、UniProt数据库筛选西南乌头有效成分的潜在靶基因,经人类孟德尔遗传综合数据库、治疗靶点数据库、GeneCards数据库、DisGeNET数据库和DRUGBANK数据库筛选心力衰竭相关疾病靶基因,两者取交集后得到西南乌头治疗心力衰竭的潜在靶基因。将西南乌头治疗心力衰竭的潜在靶基因导入STRING数据库,构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape软件对PPI网络进行分析,筛选西南乌头治疗心力衰竭核心靶基因。将西南乌头有效成分及西南乌头治疗心力衰竭核心靶基因导入Cytoscape软件构建西南乌头治疗心力衰竭的药物-有效成分-靶基因网络,使用Analyze Network计算各节点的Degree值,选取用Degree值前5位的有效成分作为西南乌头治疗心力衰竭主要活性成分。对核心靶基因进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析,采用分子对接技术分析西南乌头主要活性成分与核心靶基因的结合效能。结果共筛选得到西南乌头的有效成分靶基因819个,心力衰竭疾病靶基因2221个,取交集后获得西南乌头治疗心力衰竭的潜在靶基因326个。PPI网络共筛选出西南乌头治疗心力衰竭核心靶基因21个,分别为STAT3、AKT1、EP300、STAT1、CREBBP、PTPN11、EGFR、MAPK1、ESR1、MAPK3、HIF1A、MAPK14、TP53、PIK3CA、IL6、VEGFA、AR、JAK2、HRAS、MDM2、RELA。药物-有效成分-靶基因网络分析结果显示,西南乌头治疗心力衰竭主要活性成分为二(2-乙基己基)邻苯二甲酸酯、紫堇块茎碱、光甘草宁、紫堇达明碱和5,7-二羟基-3',4',5'-三甲氧基黄酮。GO功能及KEEG富集分析结果显示,核心靶基因主要作用于HIF-1信号通路、PI3K-AKT信号通路、MAPK信号通路等。分子对接结果�Objective To screen the main active ingredients and core target genes of Aconitum episcopale Leveille(A.episcopale)for the treatment of heart failure and to analyze their mechanisms,providing new ideas for the treatment of heart failure and the development of drug candidates.Methods The potential target genes of the active ingredients of A.episcopale were screened by searching GenBank and UniProt databases,and the target genes of heart failure-related diseas-es were screened by Human Mendelian Genetic Synthesis Database,Therapeutic Targets Database,GeneCards Database,DisGeNET Database,and DRUGBANK Database,and the intersection of the two was obtained to get the potential target genes of the A.episcopale for the treatment of heart failure.The potential target genes of A.episcopale for the treatment of heart failure were imported into the STRING database,and the protein-protein interaction(PPI)network was constructed,and the PPI network was analyzed by Cytoscape software to screen the core target genes of A.episcopale for the treatment of heart failure.The active ingredients and core target genes for the treatment of heart failure in A.episcopale were import-ed into Cytoscape software to construct a drug-active ingredient-target gene network for the treatment of heart failure in A.episcopale,and the Degree value of each node was calculated by the Analyze Network,and the active ingredients with the top 5 Degree values were selected as the main active ingredients for the treatment of heart failure in A.episcopale.The core target genes were analyzed for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the molecular docking technique was used to analysis of the binding efficacy of the main active in-gredient and the core target genes for the treatment of heart failure.Results A total of 819 active ingredient target genes of A.episcopale and 2,221 heart failure disease target genes were screened out,and 326 potential target genes were ob-tained for the treatment of heart

关 键 词：西南乌头 心力衰竭 网络药理学 分子对接 

分 类 号：R962[医药卫生—药理学]