目的 采用数据挖掘、网络药理学和分子对接技术，探讨中药抗动脉粥样硬化（AS）的用药规律、核心靶点及潜在作用机制。方法 以中国学术期刊全文数据库（CNKI）、万方数据库（Wanfang Data）、维普生物医学数据库（VIP） 3大数据库近10年治疗AS的文献为数据来源，借助古今医案云平台及Apriori关联规则函数等进行数据挖掘，以确定治疗AS的核心药物；通过TCMSP、Swiss Target Prediction数据库得到核心中药活性成分及潜在靶点，与Genecards数据库得到的疾病靶点取交集，利用Cytoscape3.10.0构建核心中药-活性成分-交集靶点网络以及蛋白质-蛋白质相互作用（PPI）网络，通过DAVID数据库进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析；对中药的核心活性成分及AS的核心靶点进行分子对接以验证其有效性。结果 从数据库中共筛选出143首方剂，涉及201味中药，药物的性味以甘、苦、辛为主，归肝、脾、心经居多。Apriori算法结果表明，“红花-桃仁-赤芍”为支持度和置信度较高的组合；通过筛选获得该组合靶点有332个，AS靶点1 663个，交集靶点228个；核心成分为黄芩素、β-谷甾醇、没食子酸120（GA120）、豆甾醇；核心靶点为肿瘤蛋白p53（TP53）、原癌基因酪氨酸蛋白激酶Src（SRC）、AKT丝氨酸/苏氨酸激酶（AKT1）、信号转导及转录活化因子3（STAT3）； GO分析条目共1 275个，KEGG通路富集分析共162条通路，根据KEGG分析，预测主要通过癌症通路、AGE-RAGE信号通路、脂质与动脉粥样硬化等信号通路发挥治疗作用；分子对接结果显示，药物核心成分与核心靶点都有一定的结合亲和力，其中SRC、AKT1靶点与分子结合较好。结论 “红花-桃仁-赤芍”通过多成分、多靶点、多通路发挥抗AS的作用，其靶点可能与TP53、SRC、AKT1、STAT3有关。

Objective To explore the dosing pattern, core targets, and potential mechanism of action of traditional Chinese medicine (TCM) against atherosclerosis (AS) using data mining, network pharmacology, and molecular docking techniques. Methods Literature from the past 10 years on AS treatment was retrieved from three major databases: China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Chinese Biomedical Database. The Ancient and Modern Medical Case Cloud Platform and Apriori association rule algorithm were used to identify core herbs for AS treatment. Active components and potential targets of core herbs were obtained from the TCMSP and Swiss Target Prediction databases. Intersection targets between herb-related targets and AS-related targets (from the Genecards database) were identified. The core herb-active component-intersection target network and protein-protein interaction (PPI) network were constructed using Cytoscape 3.10.0. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database. Molecular docking was performed to validate the binding affinity between core active components of TCM and core targets of AS. Results A total of 143 prescriptions involving 201 herbs were screened. The herbs were primarily characterized by sweet, bitter, and pungent flavors and mainly acted on the liver, spleen, and heart meridians. The Apriori algorithm indicated that the combination of Carthami Flos-Persicae Semen-Paeoniae Radix Rubra had high support and confidence levels. A total of 332 herb-related targets and 1 663 ASrelated targets were identified, with 228 intersection targets. Core active components included baicalein, β-sitosterol, gallic acid (GA120), and stigmasterol. Core targets included tumor protein p53 (TP53), proto-oncogene tyrosine-protein kinase Src (SRC), AKT serine/threonine kinase 1 (AKT1), and signal transducer and activator of transcription 3 (STAT3). GO analysis yielded 1 275 functional terms, and KEGG pathway enrichment analysis identified 162 pathways, including cancer pathways, AGE-RAGE signaling pathway, and lipid and atherosclerosis pathways. The core active components exhibited binding affinity with the core targets, with SRC and AKT1 showing particularly strong interactions. Conclusion The combination of Carthami Flos-Persicae Semen-Paeoniae Radix Rubra exerts anti-AS effects through multiple components, targets, and pathways, with potential involvement of TP53, SRC, AKT1, and STAT3. This study provides a scientific basis for the clinical application of TCM in AS treatment.

R285.5

国家自然科学基金面上项目（82274488）;2023科技创新专项（ DZMKJCX-2023-025）