目的 基于网络药理学方法分析枳术丸治疗血脂异常的药理机制，为新药研发及经典方剂临床拓展运用提供参考。方法 通过TCMSP（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform）数据库获取白术、枳实、荷叶的主要化学成分及其靶点，根据ADME筛选中药活性组分；通过Gencards、OMIM、TTD、DRUGBANK数据库获取血脂异常主要靶点，利用String平台进行蛋白质相互作用分析，构建PPI网络并挖掘网络中潜在的蛋白质功能模块。采用Metascape平台分析“药物-成分-靶点”及其参与的生物过程及通路，而后采用Cytoscape3.7.1软件构建“枳术丸成分-血脂异常靶点-通路”网络，最后通过Systems Dock Web Site进行分子对接验证。结果 枳术丸调治血脂异常的核心活性成分为槲皮素、山柰酚、木犀草素、柚皮素等，核心靶点有ESR1、NOS2、ESR2、PPARG、PTGS2、PTGS1、MAPK14、ACHE、ADRB2、F7等，分子对接验证亦显示评分大于4.25者占总数85%,大于5者占63.6%，即大部分靶点与成分的结合活性较好。枳术丸调治血脂异常的生物学通路主要作用于AGE-RAGE信号通路、HIF-1信号通路以及脂肪细胞中脂肪分解等通路，其功能主要为调节细胞内类固醇受体的生命活动等。结论 本研究初步揭示了枳术丸调治血脂异常的多成分、多靶点、多通路的作用机制，为枳术丸的临床开发利用提供基础。
Objective The pharmacological mechanism of ZHIZHU Pill in the treatment of dyslipidemia was analyzed based on the network pharmacological method, providing a reference for the development of new drugs and the clinical application of classical traditional chinese medicine prescriptions.METHODS Firstly, obtaining the main chemical composition of atractylodes, citrus aurantium and lotus leaf through the database of TCMSP.Secondly, screening of the active ingredients of traditional chinese medicines according to the ADME and acquiring ideal targets through Genecards, OMIM, TTD and DRUGBANKD databases. Thirdly, The String database was used for protein interaction analysis, building a PPI network and finding out potential protein functional modules in the network. The Metascape platform was adopted to analyze the " drug ingredients – targets–passways " and its involved biological processes and pathways. Then,Cytoscape3.7.1 software was used to construct the network of "drug ingredients – targets–passways". Finally the verification in molecular docking was performed by Systems Dock Web Site.RSEULTS: The core active ingredients of ZHIZHU Pill for regulating dyslipidemia are quercetin, kaolinol, luteolin, naringin, etc. The ideal targets are ESR1, PTGS2, NOS2, ESR2, PPARG, PTGS1, MAPK14, ACHE, ADRB2, F7, etc. The verification in Molecular docking also showed, accounting for 85% of the total had a score greater than 4.25, and 63.6% had a score greater than 5.0, which shows the binding activity of most targets and ingredients is good. The biological pathways of Zhizhu Pill in regulating dyslipidemia mainly acts on AGE-RAGE signaling pathway, HIF-1 signaling pathway and fat breakdown pathway in fat cells, and its function is mainly to regulate the life activities of steroid receptors in cells.CONCLUSIONS This study has preliminarily revealed the mechanism of ZHIZHU Pill on treating dyslipidemia with multi-components, multi-targets and multi-channels. It provides a basis for the clinical development and utilization of ZHIZHU Pill.