基于网络药理学探讨三生饮治疗缺血性脑卒中的作用机制

Exploring the Mechanism of Action of Sangshengyin in the Treatment of Ischemic Stroke Based on Network Pharmacology

摘要: 目的：利用网络药理学探究三生饮治疗缺血性脑卒中的潜在作用机制。方法：通过TCMSP数据库检索和ADME筛选三生饮中各中药的活性成分，并收集其相应靶标，与PharmMapper数据库预测的活性成分潜在作用靶标相结合，构建中药–有效成分–靶点作用网络。通过DisGeNET、GeneCards、OMIM、TTD、DrugBank数据库获取缺血性脑卒中疾病靶标后，绘制有效成分作用靶标与疾病靶标的映射关系。采用STRING平台构建三生饮治疗缺血性脑卒中潜在作用靶点间蛋白相互作用网络图、利用Cytoscape3.8.2进行可视化分析并筛选核心靶标；运用R软件3.6.3进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。结果：筛选出了三生饮19个有效成分(β-谷甾醇、谷甾醇、二氢辣椒素、丁子香萜、石防风素等)，48种有效成分与疾病的交集靶点，PPI中5个核心靶标(ALB, JUN, PTGS2, MAPK1, ANXA5)。GO功能注释得到生物学过程条目997条(如血清素受体信号通路、细胞的激素代谢、细胞对类固醇激素和金属离子的反应等)，细胞组成条目67条(如细胞膜区、膜微结构域、膜筏、细胞窖等)，分子功能条目107条(如核受体活性、神经递质型G蛋白偶联受体活性、类固醇激素受体活性等)；KEGG通路富集分析确定了118条三生饮治疗缺血性脑卒中的通路(如cAMP信号通路、IL-17信号通路、TNF信号通路等、神经营养因子相关信号通路等)。结论：本研究从多靶标、多通路阐释了三生饮可能通过抗氧化应激、抗炎、抗凋亡、促进细胞存活等生物学过程，发挥抗缺血性脑损伤作用，为后续对本方的深入研究提供了理论依据。

Abstract: Objective: To investigate the potential mechanism of action of Sangshengyin in the treatment of is-chemic stroke based on network pharmacology. Methods: The active ingredients of each herbal medicine in Sangshengyin were searched by TCMSP database and screened by ADME, and their corresponding targets were collected and combined with the potential targets of active ingredients predicted by PharmMapper database to construct a herbal medicine-active ingredient-target action network. After obtaining the ischemic stroke disease targets through DisGeNET, GeneCards, OMIM, TTD and DrugBank databases, the mapping relationships between the active ingredient targets and disease targets were drawn. The STRING platform was used to construct a protein interaction net-work between the potential targets of Sanshengyin for ischemic stroke, and Cytoscape3.8.2 was used to visualize and screen the core targets; R software 3.6.3 was used to enrich the gene ontology (GO) function and Kyoto Encyclopedia of Genomes (KEGG) pathway. Results: Nineteen active ingre-dients (β-sitosterol, Stigmasterol, Dihydrocapsaicin, Mairin, Deltoin, etc.), 48 active ingredi-ent-disease intersection targets, and 5 core targets in PPI (ALB, JUN, PTGS2, MAPK1, ANXA5) were screened. 997 entries of biological processes were obtained from GO functional annotation (e.g. ser-otonin receptor signaling pathway, cellular hormone metabolism, cellular response to steroid hor-mones and metal ions, etc.), 67 entries for cellular composition (e.g. cellular membrane regions, membrane microdomains, membrane rafts, caveola, etc.) and 107 entries for molecular functions (e.g. nuclear receptor activity, neurotransmitter-type G protein-coupled receptor activity, steroid hormone receptor activity, etc.); the KEGG pathway enrichment analysis identified 118 pathways (e.g. cAMP signaling pathway, IL-17 signaling pathway, TNF signaling pathway, neurotrophic fac-tor-related signaling pathway, etc.) for the treatment of ischemic stroke. Conclusion This study il-lustrates that Sanshengyin may exert anti-ischemic brain injury effects through antioxidant stress, anti-inflammatory, anti-apoptotic and cell survival biological processes, and provides a theoretical basis for further research on this formula.