目的 应用网络药理学方法对雷公藤多苷引起睾丸损伤机制进行研究，探讨潜在靶点和作用机制，并进行动物实验验证，为后续该药物的合理使用提供新的研究策略。方法 依托文献查询和TCMSP、GeneCards、OMIM、Metascape数据库挖掘雷公藤多苷中有效成分信息，挑选主要药物活性成分及与睾丸损伤相关性靶点，构建蛋白相互作用（PPI）网络。使用Metascape数据库对核心靶点进行基因本体（GO）基因注释及京都基因与基因百科全书（KEGG）通路富集分析，并进行分子对接和动物实验验证。结果 共筛选出雷公藤多苷18个活性成分，其中雷酚萜醇、苯代南蛇碱、雷公藤对醌A等为主要活性成分；雌激素受体1（ESR1）、表皮生长因子受体（EGFR）等为核心靶点；KEGG富集分析雷公藤多苷活性成分作用于睾丸损伤的通路主要涉及癌症信号通路、cAMP信号通路、Ras信号通路等；网络药理学与分子对接结果分析显示呋喃南蛇碱与蛋白激酶B1（Akt1）结合良好，雷公藤对醌A与肿瘤坏死因子（TNF）结合良好，苯代南蛇碱与ESR1结合良好；动物实验中雷公藤多苷组ESR1、EGFR mRNA表达水平显著升高（P＜0.05）。结论 雷公藤多苷致睾丸损伤的机制可能与核心靶点ESR1、EGFR等密切相关。

Objective To investigate the mechanism of testicular injury induced by tripterygium glycosides by network pharmacology, explore the potential targets and mechanism of action, and conduct animal experiments to verify it, so as to provide a new research strategy for the rational use of the drug. Methods Based on literature search and TCMSP, GeneCards, OMIM, and Metascape databases, the information of active ingredients in tripterygium glycosides was mined, and the main active ingredients and targets associated with testicular injury were selected to construct the protein interaction (PPI) network. Metascape database was used to conduct gene ontology (GO) gene annotation and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analysis for core targets, and molecular docking and animal experiments were conducted. Results A total of 18 active components of tripterygium glycosides were screened, among which the main active components were triptonoterpenol, celabenzine, triptoquinone A. Estrogen receptor 1 (ESR1) and epidermal growth factor receptor (EGFR) were the core targets. KEGG enrichment analysis of the active components of tripterygium glycosides on testicular injury mainly involved cancer signaling pathway, cAMP signaling pathway, Ras signaling pathway, etc. The results of network pharmacology and molecular coupling analysis showed that celafurine was well bound to protein kinase B1 (Akt1), triptoquinone A was well bound to tumor necrosis factor (TNF), and celabenzine was well bound to ESR1. The mRNA expression levels of ESR1 and EGFR in tripterygium glycosides group were significantly increased (P < 0.05). Conclusion Mechanism of testicular injury induced by tripterygium glycosides may be closely related to the core targets such as ESR1 and EGFR.

R285；R287.3