[关键词]
[摘要]
目的基于“方-证”关联的研究思路,系统阐释身痛逐瘀汤(STZYD)治疗痹证的化学物质基础、作用靶点及生物网络机制,并探讨其“异病同治”的科学内涵。方法采用高效液相色谱-四极杆飞行时间质谱(HPLC-Q-TOF-MS/MS)对STZYD化学成分进行系统表征与辨识;选取33个主要活性成分为研究对象,利用Swiss Target prediction与Pharmmapper数据库收集活性成分的候选靶标;通过SoFDA与SymMap数据库,收集痹证的证候基因集,借助STRING 12.0平台构建痹证相关基因与STZYD候选靶标交集的蛋白质-蛋白质相互作用(PPI)网络,筛选核心靶点,并通过Cytoscape3.10.3软件构建网络图;利用Metascape在线对交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;运用SoFDA平台预测交集靶点的现代医学症状,并与痹证相关现代医学疾病相对应,构建“靶点-通路-药理作用-疾病”关联网络。结果 STZYD中共鉴定出244个化学成分;选取的33个活性成分治疗痹证的潜在作用靶点共190个,PPI网络分析发现白细胞介素-6(IL6)、肿瘤坏死因子(TNF)、白细胞介素-1β(IL1B)、信号转导子和转录激活子3(STAT3)、表皮生长因子受体(EGFR)等可能为核心靶点; KEGG筛选出与痹证密切相关的通路共70条,包括磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K)、核因子-κB(NF-κB)、白细胞介素17(IL-17)等信号通路;病-证关联结果显示,STZYD可能对痹证相关骨关节病、自身免疫性疾病等具有治疗作用。结论 STZYD可通过多成分、多靶点、多通路的协同作用,干预炎症反应、免疫调节、血管生成等过程,体现了“瘀血痹阻证”与多种现代疾病之间的内在关联,为“异病同治”理论提供了现代生物学依据。
[Key word]
[Abstract]
Objective Based on the research idea of “prescription-syndrome correlation”, the study systematically elucidates the chemical material basis, action targets and biological network mechanism of Shentong Zhuyu Decoction (STZYD) in the treatment of bi syndrome, and explores the scientific connotation of its “treating different diseases with the same therapy”. Methods HPLC-QTOF-MS/MS was used to systematically characterize and identify the chemical components of STZYD. A total of 33 main active ingredients were selected as the research objects, and the potential targets of the compounds were collected by Swiss Target Prediction and PharmMapper databases. The syndrome-related gene sets of bi syndrome were retrieved from the SoFDA and SymMap databases. The protein-protein interaction (PPI) network of the common targets between bi syndrome-related genes and STZYD candidate targets was constructed by STRING 12.0 platform, and the core targets were screened and visualized by Cytoscape 3.10.3 software. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersection targets was performed online by Metascape. The modern medical symptoms of the intersection targets were predicted by the SoFDA platform and corresponded to the modern medical diseases related to bi syndrome, so as to construct a “targets-pathways-pharmacological effects-diseases” association network. Results A total of 244 chemical components were identified in the STZYD sample. 190 potential therapeutic targets of the 33 selected active components against bi syndrome were identified. PPI network analysis revealed that interleukin-6 (IL6), tumor necrosis factor (TNF), interleukin-1β (IL1B), signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) might be the core targets. KEGG pathway enrichment analysis identified 70 pathways closely associated with bi syndrome, including phosphatidylinositol 3-kinase protein kinase B signaling pathway, nuclear factor-κB signaling pathway, and interleukin-17 signaling pathway. The disease-syndrome association results indicate that STZYD may have therapeutic effects on osteoarticular diseases and autoimmune diseases related to bi syndrome. Conclusion STZYD can intervene in processes such as inflammatory response, immune regulation, and angiogenesis through the synergistic effect of multi-component, multi-target and multi-pathway, which reflects the intrinsic correlation between “syndrome of static blood blocking collaterals” and various modern diseases, and provides a modern biological basis for the theory of “treating different diseases with the same therapy”.
[中图分类号]
R285.5
[基金项目]
国家科技重大专项-“四大慢病重大专项”(2025ZD0549700);安徽省科技重大专项资助(202303a07020007)