目的 基于网络药理学与分子对接技术，探究诃子提高耐缺氧能力的相关靶点及通路，并探讨其潜在作 用机制。方法 收集诃子活性成分，通过 SwissTarget Prediction 平台预测诃子活性成分的潜在靶点。通过 Genecards、OMIM数据库收集缺氧相关疾病基因。两者取交集后，用STRING、Cytoscape程序建立蛋白-蛋白相 互作用（PPI）网络系统，检索相关性强的关键基因，并完成基因本体（GO）及京都基因与基因组百科全书 （KEGG）富集分析研究。进一步构建“中药-活性成分-关键基因-通路”网络，选取网络中度值排前5位的核心基 因及排前5位的核心成分，用AutoDockTools、Pymol程序对有对应关系的蛋白和分子进行对接验证。结果 收集得 到诃子潜在活性成分30个，提高耐缺氧能力潜在靶点312个。筛选得到关键基因为TNF、IL-6、ESR1、Bcl-2、 Caspase-3、 ALB、 HIF-1α、 JUN、 STAT3 和 NF- κB1。 KEGG 富 集 分 析 得 到 Prostate cancer（前 列 腺 癌）， AGE-RAGE signaling pathway in diabetic complications（糖尿病 AGE-RAGE 信号通路），HIF-1 signaling pathway （HIF-1信号通路），Lipid and atherosclerosis（脂质和动脉粥样硬化），PI3K-Akt signaling pathway（PI3K-Akt信号 通路）和Pathways in cancer（癌症通路）等信号通路。分子对接结果显示，诃子核心活性成分与核心基因之间的结合性 良好。结论 诃子可通过多靶点、多通路发挥提高耐缺氧能力活性，该机制可为诃子提高耐缺氧能力方面的应 用及药物研发提供理论依据。

Objective To explore the related targets and pathways of improving hypoxia tolerance of Chebulae Fructus and its potential mechanism of action based on network pharmacology and molecular docking technology. Methods The active ingredients of Chebula Fructus were collected and the potential targets of active ingredients in Chebula Fructus were predicted by SwissTarget Prediction platform. Hypoxia-related genes were collected from Genecards and OMIM databases. After the intersection of the two，the protein-protein interaction（PPI）network system was established by STRING and Cytoscape programs， key genes with strong correlation were searched， and Gene Ontology（GO）and Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis were completed. The "TCM - active ingredients - key genes - pathways" network was further constructed，and the top 5 core genes and the top 5 core components ranking by degree values of the network were selected， and the docking verification of corresponding proteins and molecules were performed by AutoDock Tools and Pymol programs. Results A total of 30 potential active ingredients of Chebulae Fructus and 312 potential targets for improving hypoxia tolerance were collected. The key genes were TNF， IL-6，ESR1，Bcl-2，Caspase-3，ALB，HIF-1α，JUN，STAT3 and NF-κB1. KEGG enrichment analysis was used to obtain prostate cancer，AGE-RAGE signaling pathway in diabetic complications. HIF-1 signaling pathway，lipid and atherosclerosis，PI3K-Akt signaling pathway，and pathways in cancer. Molecular docking results showed that the core active ingredients of Chebulae Fructus were well combined with the core genes. Conclusion Chebulae Fructus can exert the activity of enhancing hypoxia tolerance through multi-target and multi-pathway. The mechanism in this study can provide theoretical basis for the application of improving hypoxia tolerance and drug development of Chebulae Fructus.

R285.5

陕西省中医药管理局项目计划 （2021-ZZ-ZY001）；军队后勤科研重点项目 （BKJ23WSIJ006）；联勤保障部队第九四○医院院内项目 （2021yxky060）