基于网络药理学探讨葛根治疗臂丛神经损伤机制

Explorating mechanism of Puerariae Lobatae Radix in the treatment of brachial plexus injury based on network pharmacology

目的:基于网络药理学对葛根治疗臂丛神经损伤(Brachial Plexus Injury,BPI)的主要活性成分以及潜在分子机制进行探讨。方法:通过中药系统药理学技术平台(TCMSP)数据库筛选葛根的活性成分及作用靶点,采用人类基因组注释数据库GeneCards、Disgenet和在线人类孟德尔遗传数据库OMIM检索BPI的相关治疗靶点。利用STRING平台构建蛋白质-蛋白质相互作用网络并筛选交集关键靶点。运用Cytoscape 3.7.2建立“疾病-靶标-药物-成分”网络模型。利用DAVID 6.8平台的基因本体论(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析功能,分析交集靶点。结果:通过检索GeneCards、Disgenet和OMIM三个数据库最终获得4个药物活性成分和291个潜在靶点,与BPI交集的关键靶点69个,GO分析得到1 669个条目,KEGG分析获得106条信号通路。结论:利用网络药理学客观地分析了葛根治疗BPI的机制可能是通过丝裂原活化蛋白激酶3(Mitogen-activated Protein Kinase 3,MAPK3)、半胱氨酸蛋白酶(Caspase,CASP)3、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等关键分子共同参与到抑制炎症反应的过程,通过抗炎,抗氧化应激,缓解钙超载,调节钙信号通路,并调节血管内皮生长因子信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/丝苏氨酸蛋白激酶(AKT Serine/Threonine Kinase,AKT)信号通路、TNF信号通路信号通路等生物学过程来发挥治疗作用。葛根通过多靶点、多种信号通路协同调控BPI相关生物进程,从而达到治疗BPI的目的,为后续深入探究葛根治疗BPI的分子机制提供了理论依据,同时为今后创新药物的研制开发提供了新的思路和方向。

Objective: To explore the potential molecular mechanism of Gegen(Puerariae Lobatae Radix) in the treatment of brachial plexus injury based on network pharmacology. Methods: The active components and targets of Gegen were screened by TCMSP database, and the targets of brachial plexus injury were searched by Gene Cards, Disgenet and OMIM database. Cytoscape 3.7.2 software was used to construct the “drug-component-target-disease” network diagram. The PPI network was constructed by STRING platform, and strategic targets were screened. The GO function analysis and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes were performed on the intersection targets by DAVID 6.8 Platform. Results: Four drug components and 291 potential targets were achieved, 69 intersection targets with brachial plexus injury were generated, 1 669 items were obtained by the GO function analysis, 106 signaling pathways were obtained by the KEGG analysis. Conclusion: The mechanism of Gegen in the treatment of brachial plexus injury may be performed by MAPK3, CASP3, TNF, EGFR and other key molecules, which participate in antiinflammatory response, reducing oxidative stress, relieving calcium overload, regulating calcium signaling pathway, and controlling VEGF signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway. Gegen sympathetically participates in the treatment of brachial plexus injury through multi-target regulation of multiple signaling pathways, which provides a theoretical basis for further exploring its molecular mechanism and some ideas for the development of novel drugs.