目的 采用网络药理学、毒理学及分子对接分析技术探究附子治疗骨关节炎的作用机制及其毒性反应。方法 运用TCMSP、ETCM、GeneCards、OMIM、CTD数据库，获取附子的活性成分、作用靶点及产生毒性反应的核心靶点；通过Venny、Cytoscape观察化合物与靶点的相互作用，并运用DAVID数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。最后结合Autodock软件进行分子对接以进一步验证。结果 共获得附子22种化合物、500个作用靶点及2 856个附子诱导的毒性靶点。附子的主要活性成分可能作用于肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、蛋白激酶B1（Akt1）、胱天蛋白酶-3（CASP3）等核心靶点，主要涉及磷脂酰肌醇3激酶（PI3K）/Akt、TNF等信号通路调控骨关节炎及其毒性反应。分子对接预测关键活性成分与TNF、IL-6等靶蛋白均具有较好的结合亲和力。结论 附子可调节PI3K/Akt、TNF等信号通路干预炎症反应、细胞凋亡治疗骨关节炎，同时在其治疗过程中体现了毒效双重性。

Objective To investigate the therapeutic mechanism of Aconiti Lateralis Radix Praeparata in treatment of osteoarthritis, and its concomitant toxic reactions based on network pharmacology, toxicology, and molecular docking techniques. Methods To identify active components of Aconiti Lateralis Radix Praeparata, and its therapeutic and core toxicity targets by TCMSP, ETCM, GeneCards, OMIM, and CTD. Compound-target interactions were visualized using Venny 2.1.0 and Cytoscape 3.9.1. The intersecting targets were further analyzed by GO and KEGG pathway enrichment using DAVID database, and finally molecular docking was verified with Autodock software. Results A total of 22 active compounds, 500 therapeutic targets, and 2 856 toxicity-related targets of Aconiti Lateralis Radix Praeparata were identified. The primary active components of Aconiti Lateralis Radix Praeparata may target key entities such as TNF, IL-6, Akt1, and CASP3. These interactions predominantly involve the regulation of osteoarthritis and its toxic responses through signaling pathways including the PI3K/Akt pathway, TNF pathway. Molecular docking revealed that key active components possess good binding affinity with the TNF and IL-6 target proteins.Conclusion Aconiti Lateralis Radix Praeparata can regulate the PI3K/Akt and TNF signaling pathways to intervene in inflammatory responses and cell apoptosis, thereby treating osteoarthritis. At the same time, during its treatment process, it exhibits the dual characteristics of toxicity and efficacy.

R285.5;R287.2

国家自然科学基金资助项目（82160416）