基于网络药理学研究二仙汤加减方治疗脊髓损伤的作用机制  

Mechanism of Modified Erxian Decoction in Treating Spinal Cord Injury Based on Network Pharmacology

作　　者：李二亮 晏荣保 闫康 赵宁侠 黄汝芹 马琼 赵海恩 廖博 LI Erliang;YAN Rongbao;YAN Kang;ZHAO Ningxia;HUANG Ruqin;MA Qiong;ZHAO Haien;LIAO Bo(Department of Orthopaedics,the Second Affiliated Hospital of Air Force Military Medical University,Xi′an 710038,China;Department of Traditional Chinese Medicine,the Second Affiliated Hospital of Air Force Military Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学第二附属医院骨科,西安710038 [2]空军军医大学第二附属医院中医科,西安710038

出　　处：《世界中医药》2022年第18期2529-2534,共6页World Chinese Medicine

基　　金：国家自然科学基金面上项目(82174166)——二仙汤加减方剂通过PI3K/Akt通路调节轴突再生促进脊髓损伤的修复机制研究。

摘　　要：目的:基于网络药理学等方法探讨二仙汤加减方治疗脊髓损伤(SCI)的有效性及相关机制。方法:在动物层面验证方剂的有效性,然后通过网络药理学方法进行化合物、靶点预测和网络分析,根据中药系统药理学数据库与分析平台(TCMSP)和UniProt数据库选择方剂的化学成分和靶标,并从GeneCard和Drugbank数据库中收集SCI的治疗靶标。使用String数据库分析蛋白质-蛋白质相互作用。然后利用Cytoscape_v3.7.1构建网络,利用Metascape数据库进行基因本体富集分析和京都基因和基因组百科全书富集分析。结果:动物实验显示二仙汤加减可明显缓解脊髓损伤,增加大鼠后肢行为学评分。网络药理学研究结果表明二仙汤加减方剂中18味中药共检索到5353个基因,去重筛选后共获得319个基因,共检索到SCI靶基因3237个基因,去重后共获得2638个基因,二者共表达基因216个。方剂中的川芎、当归、丹参、香附、延胡索、淫羊藿、郁金等关键活性成分可能通过AKT1、MAPK3、NFKBIA、FOS、PIK3CG等关键基因介导cAMP、PI3K/AKT、MAPK、TNF等信号通路,起到治疗SCI的作用。结论:二仙汤加减对SCI治疗效果显著,网络药理学研究表明了多靶点、多组分二仙汤加减可能通过cAMP信号通路、PI3K/AKT信号通路发挥治疗SCI的作用。Objective:To explore the effectiveness and mechanism of modified Erxian Decoction(MED)in the treatment of spinal cord injury(SCI)based on network pharmacology and other methods.Methods:The effectiveness of the prescription was verified via animal experiments.The component and target prediction and network analysis were carried out with the methods of network pharmacology.The chemical components and targets of the prescription were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and UniProt,and the therapeutic targets of SCI were collected from GeneCards and Drugbank.The protein-protein interaction was analyzed in String and then Cytoscape_v3.7.1 was used to build a network.Metascape was used for gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Results:The animal experiments showed that MED significantly alleviated SCI and increased the behavioral score of hindlimb in rats.A total of 5353 genes were identified to be associated with the 18 Chinese herbal medicines in MED.After re-screening,319 genes were obtained.A total of 3237 genes were screened out for SCI,among which 2638 remained after re-screening.MED and SCI shared 216 common genes.Chuanxiong Rhizoma,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Cyperi Rhizoma,Corydalis Rhizoma,Epimedii Folium,and Curcumae Radix in the prescription may mediate the cyclic adenosine monophosphate(cAMP),phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt),mitogen-activated protein kinase(MAPK),and tumor necrosis factor(TNF)signaling pathways through AKT serine/threonine kinase 1(AKT1),MAPK3,nuclear factor-kappa-B-inhibitor alpha(NFKBIA),Fos proto-oncogene,AP-1 transcription factor subunit(FOS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)and other key genes to treat SCI.Conclusion:MED has significant effect on the treatment of SCI.The network pharmacology-based study indicates that the multi-target and multi-component MED may

关 键 词：脊髓损伤 二仙汤加减 网络药理学 中药 富集分析 PI3K/AKT信号通路 cAMP信号通路 

分 类 号：R285[医药卫生—中药学] R289.4[医药卫生—中医学] R641