目的 基于网络药理学方法探究黄芪-桂枝药对防治化疗引起的神经毒性的作用机制。方法 通过中药系统药理学数据库分析平台（TCMSP）在线平台获取黄芪与桂枝的潜在活性成分及及其作用靶点，利用GeneCards数据库检索与化疗引起的神经毒性相关靶点，将上述二者共有的靶点输入STRING数据库，获取蛋白质-蛋白质相互作用（protein-protein interaction network，PPI）网络；通过Cytoscape 3.2.1软件中CytoNCA插件筛选潜在核心靶点，并构建“活性成分-核心靶点-疾病”网络；通过DAVID在线软件进行基因本体（gene ontology，GO）功能富集分析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。结果 黄芪-桂枝药对经筛选得到38个潜在活性成分和442个潜在作用靶点，其中与化疗引起的神经毒性共同作用的靶点有242个，通过拓扑学层面挖掘得到核心靶点46个。GO功能富集分析发现黄芪-桂枝药对防治化疗引起的神经毒性主要与基因的转录表达、细胞凋亡及对药物的反应等相关。KEGG通路富集分析发现黄芪-桂枝药对防治化疗引起的神经毒性主要与癌症相关信号通路、乙型肝炎通路及磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinases，PI3K）-蛋白激酶B（protein kinase B，Akt）信号通路等相关。结论 黄芪-桂枝药对能够通过多成分、多靶点、多途径的作用方式，从基因的转录表达、细胞凋亡等方面发挥防治化疗引起的神经毒性的作用。

Objective To explore the mechanism of Astragali Radix and Cinnamomi Ramulus on preventing and treating neurotoxicity caused by chemotherapy based on network pharmacology. Methods Active ingredients and targets of Astragali Radix and Cinnamomi Ramulus were obtained through TCMSP, neurotoxicity caused by chemotherapy-related targets were searched by Gene Cards database, common targets from both screenings were input into STRING database to construct protein-protein interaction (PPI) network. Potential core targets were screened through CytoNCA plug-in in Cytoscape 3.2.1 software, and “active ingredients-core targets-diseases” network was constructed; DAVID online software was used to perform gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Results A total of 38 potential active ingredients and 442 potential targets were obtained from Astragali Radix and Cinnamomi Ramulus, of which 242 targets co-acted with neurotoxicity caused by chemotherapy, and 46 core targets were obtained through topological mining. GO function enrichment analysis revealed that effect of Astragali Radix and Cinnamomi Ramulus on preventing and treating neurotoxicity caused by chemotherapy was mainly related to gene transcription, cell apoptosis, and drug response. Enrichment analysis of the KEGG pathway found that effect of Astragali Radix and Cinnamomi Ramulus on preventing and treating neurotoxicity caused by chemotherapy was mainly related to cancer-related signaling pathways, hepatitis B pathways, and phosphatidylinositol 3-kinases (PI3K)-protein kinase B (Akt) signaling pathway. Conclusion Astragali Radix and Cinnamomi Ramulus can prevent and treat neurotoxicity caused by chemotherapy in terms of gene transcription and cell apoptosis through a multi-component, multi-target and multi-channel action mode.

R285.5

天津市科技计划项目（18ZXXYSY00130）