【摘要】 目的 运用网络药理学和免疫浸润的方法研究红花注射液治疗肝细胞癌(HCC)的分子机制。方法 通过已发表的文献收集红花注射液主要有效成分，利用数据库预测红花注射液的成分靶点与HCC的靶点，借助Cytoscape 3.8.0构建“中药-成分-靶点-疾病”网络，利用STRING数据库和Cytoscape软件构建蛋白互作PPI网络并筛选关键靶点，运用CytoMCODE插件完成模块分析。应用R软件对共有靶点进行GO和KEGG富集分析，并构建“成分-靶点-通路”网络。通过TRRUST和MetaScape数据库进行转录因子及相关调控基因特异富集。利用GEPIA数据库对关键靶点进行表达差异分析和生存预后分析，最后利用TIMER数据库进行肿瘤细胞的免疫浸润分析。结果 筛选出27种红花注射液有效成分和123个作用靶点，可通过介导癌症信号通路、Toll样受体、IL-17、TNF等炎症相关通路以及MAPK、PI3K-Akt等信号通路发挥抗肝细胞癌作用。探寻到11个相关转录因子。免疫浸润分析表明，ESR1表达水平与B细胞、CD8~+T细胞、CD4~+T细胞等细胞的免疫浸润水平呈负相关(P<0.05);SRC则相反，呈正相关。结论 本研究初步揭示了红花注射液治疗肝细胞癌的多成分、多靶点、多通路的作用机制，ESR1、SRC等靶点可能在治疗过程发挥重要作用。更多还原

【Abstract】 Objective Network pharmacology and immune infiltration was used to investigate the molecular mechanism of the Honghua Injection for hepatocellular carcinoma treatment. Methods Main active components in Honghua injection were retrieved from published literature and the constituent targets of Honghua Injection and the targets of HCC were predicted by database. The “Traditional Chinese medicine-component-target-disease” network was constructed with Cytoscape 3.8.0. The target protein interaction(PPI) network was constructed based on the STRING database and Cytoscape software, the key targets were screened as well, and the module analysis was conducted by CytoMCODE plug-in. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the common target were performed using R software, and a “Component-target-pathway” network was constructed. The transcription factors and related regulatory genes were specifically enriched by TRRUST and Metascape database. GEPIA database was used to analyze the expression differences and survival prognosis of key targets, and then TIMER database was used to analyze the immune infiltration of tumor cells. Results The results found Honghua injection have 27 active components and 123 targets related to hepatocellular carcinoma. Through mediating the cancer signaling pathways, the Toll-like receptor, IL-17, TNF inflammation-related pathways, and MAPK, PI3K-Akt signaling pathways by these compounds, Honghua injection plays an important role in treating hepatocellular carcinoma. The expression level of CSRP1 was negatively correlated with the immune infiltration level of B Cell, CD8~+ T Cell, CD4~+ T Cell, Macrophage, Neutrophil and Dedntritic Cell(P<0.05), while the expression level of SRC was the opposite.Conclusion This study has preliminarily revealed the mechanism of Honghua injection on treating hepatocellular carcinoma with multi-components, multi-targets and multi-channels. ESR1,SRC and other targets may play an important role in the treatment process.更多还原