【摘要】 目的 通过网络药理学方法探讨芍药甘草汤治疗肝癌癌痛的作用机制。方法 利用中药系统药理学数据库与分析平台筛选芍药甘草汤的主要活性成分及其对应的作用靶点，通过GeneCards、OMIM、DrugBank数据库检索肝癌、癌痛的相关靶点。使用Venny 2.1.0获取药物活性成分靶点与肝癌、癌痛靶点的交集靶点，通过Cytoscape 3.7.1软件构建药物活性成分-肝癌-癌痛靶点网络并行网络拓扑分析。使用STRING平台对交集靶点进行蛋白质-蛋白质互相作用(PPI)网络分析，使用Cytoscape 3.7.1软件筛选关键靶点。利用Metascape平台针对交集靶点进行基因本体论功能富集分析及京都基因和基因组百科全书功能富集分析。结果 共筛选出芍药甘草汤活性成分93种及其对应靶点231个，获得肝癌相关靶点1 498个、癌痛相关靶点1 873个。取交集后获得交集靶点125个，芍药甘草汤作用于肝癌癌痛靶基因的映射率为5.1%。芍药甘草汤中治疗肝癌癌痛的主要活性成分有槲皮素、山柰酚、柚皮素等；关键靶点有原癌基因JUN、肿瘤坏死因子、信号转导子和转录激活剂3、白细胞介素(IL)-1β、IL-6、IL-4、C-X-C基序趋化因子配体8、C-C基序趋化因子2、丝裂原活化蛋白激酶3、肿瘤蛋白P53等。交集靶点涉及的通路主要包括癌症通路、糖尿病并发症中的糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、IL-17信号通路、缺氧诱导因子1(HIF-1)信号通路等。结论 芍药甘草汤可能通过槲皮素、山柰酚、柚皮素等活性成分作用于原癌基因JUN、肿瘤坏死因子、信号转导子和转录激活剂3等相关靶点，影响AGE-RAGE、IL-17、HIF-1等通路，阻止肝癌细胞增殖，减少致痛介质释放，缓解因肿瘤生长引起的牵涉痛及炎性因子相关性疼痛，从而达到治疗肝癌癌痛的目的。更多还原

【Abstract】 Objective To explore the mechanism of action of Shaoyao Gancao Decoction in the treatment of liver cancer-caused cancerous pain by the network pharmacology method.Methods The main active ingredients of Shaoyao Gancao Decoction and their corresponding action targets were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the targets related to liver cancer or cancerous pain were searched through GeneCards, OMIM and DrugBank databases. Venny 2.1.0 was used to obtain the intersection targets between active pharmaceutical ingredient targets and liver cancer/cancerous pain targets. The active pharmaceutical ingredients-liver cancer-cancerous pain target network was established and a network topology analysis was conducted using Cytoscape3.7.1 software. STRING platform was employed to perform a protein-protein interaction(PPI) network analysis on the intersection targets, and Cytoscape 3.7.1 software was used to screen key targets. Metascape platform was utilized to perform Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the intersection targets.Results A total of 93 active ingredients of Shaoyao Gancao Decoction and their 231 corresponding targets were screened out, and 1 498 liver cancer-related targets and 1 873 cancerous pain-related targets were obtained. After the intersection, 125 intersection targets were obtained, and the mapping rate of Shaoyao Gancao Decoction taking effect on the target genes of liver cancer-caused cancerous pain was 5.1%. The main active ingredients of Shaoyao Gancao Decoction for treating liver cancer-caused cancerous pain included quercetin, kaempferol, naringenin, etc.; the key targets included protooncogene JUN, tumor necrosis factor, signal transducer and activator of transcription 3, interleukin(IL)-1β, IL-6, IL-4, C-X-C motif chemokine ligand 8, C-C motif chemokine 2, mitogen-activated protein kinase 3, tumor protein P53, etc. The pathways which the intersection targets involved mainly included cancer pathway, advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE) signaling pathway in diabetic complications, IL-17 signaling pathway, hypoxia-inducible factor 1(HIF-1) signaling pathway, etc.Conclusion Shaoyao Gancao Decoction might exert the effects on the related targets such as protooncogene JUN, tumor necrosis factor, and signal transducer and activator of transcription 3 via the active ingredients including quercetin, kaempferol and naringenin, affect the pathways such as AGE-RAGE, IL-17 and HIF-1, inhibit liver cancer cell proliferation, reduce the release of algogenic substances, and ameliorate tumor growth-caused referred pain and inflammatory factor-related pain, thus achieving the goal of treating liver cancer-caused cancerous pain.更多还原