目的 基于网络药理学及动物实验探讨荆防颗粒对自身免疫性肝炎（autoimmune hepatitis，AIH）小鼠的治疗作用及作用机制。方法 通过TCMSP数据库筛选荆防颗粒的活性成分及其对应的靶点，通过检索Omim、Drugbank和GeneCards数据库收集AIH相关的靶点，进而得到荆防颗粒治疗AIH的关键靶点；将获得的关键靶点导入STRING数据库进行分析，并构建蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络，通过Cytoscape软件可视化；通过Metascape数据库对关键靶点进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。通过建立刀豆蛋白A诱导的AIH小鼠模型探讨荆防颗粒治疗AIH的作用机制。结果 共筛选得到荆防颗粒中159个潜在活性成分和269个相关的靶点，与343个AIH相关靶点取交集，获得25个交集靶点。PPI网络分析显示，白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、IL-1β、信号传导和转录激活蛋白3（signal transducer and activator of transcription 3，STAT3）和IL-8/CXC型趋化因子配体8（CXC chemokine ligand 8，CXCL8）等靶点可能为荆防颗粒治疗AIH的关键靶点；KEGG通路富集分析得到炎症途径和凋亡相关途径信号通路。体内实验结果显示，与模型组比较，荆防颗粒显著减轻了刀豆蛋白A诱导的肝炎，表现为小鼠存活率增加、肝细胞坏死减少、血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）和天冬氨酸氨基转移酶（aspartate aminotransferase，AST）活性降低（P＜0.05、0.01）；荆防颗粒还通过抑制IL-6/STAT3、NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）/IL-1β和TNF-α/核因子-κB（nuclear factor-κB，NF-κB）通路进而调节多种细胞因子（IL-6、IL-1β、TNF-α、CXCL-8）的产生（P＜0.05、0.01），从而发挥抗炎、抗凋亡作用。结论 荆防颗粒通过多成分、多靶点发挥治疗AIH的作用。

Objective To explore the therapeutic effect and mechanism of Jingfang Granules (荆防颗粒) on autoimmune hepatitis (AIH) mice based on network pharmacology and animal experiments. Methods The active components of Jingfang Granules and corresponding targets were screened by TCMSP database, and targets related to AIH were collected by Omim, Drugbank and GeneCards databases, and then the key targets of Jingfang Granules in treating AIH were obtained. The obtained key targets are imported into STRING database for analysis, and protein-protein interaction (PPI) network was constructed and visualized by Cytoscape software. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of key targets were analyzed by Metascape database. AIH mice model induced by concanavalin A was established to explore the mechanism of Jingfang Granules in treating AIH. Results A total of 159 potential active components and 269 related targets in Jingfang Granules were screened, and 25 intersecting targets were obtained by intersecting with 343 AIH related targets. PPI network analysis showed that interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, signal transducer and activator of transcription 3 (STAT3) and IL-8/CXC chemokine ligand 8 (CXCL8) may be the key targets of Jingfang Granules in treating AIH. KEGG pathway enrichment analysis obtained inflammatory pathway and apoptosis-related pathway signal pathway. The experimental results in vivo showed that compared with model group, Jingfang Granules significantly reduced the hepatitis induced by concanavalin A, which showed that survival rate of mice was increased, necrosis of hepatocytes was decreased, activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were decreased (P < 0.05, 0.01). Jingfang Granules regulated the production of multiple cytokines including IL-6, IL-1β, TNF-α and CXCL-8 by inhibiting IL-6/STAT3, NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1β and TNF-α/nuclear factor-κB (NF-κB) pathways (P < 0.05, 0.01), thereby playing an anti-inflammatory and anti-apoptosis role. Conclusion Jingfang Granules plays a role in treating AIH through multi-components and multi-targets.

R285.5

国家“重大新药创制”科技重大专项（2021CXGC010508）