银杏叶调控TNF/NF-κB信号通路干预血栓闭塞性脉管炎的网络药理学研究  

Network Pharmacology Research of Ginkgo Folium Intervening Thromboangiitis Obliterans Disease by Regulating TNF/NF-κB Signaling Pathway

作　　者：王玉涛[1,2] 郇晓宇 郭建壮 WANG Yutao;HUAN Xiaoyu;GUO Jianzhuang(Shandong University of Traditional Chinese Medicine,Jinan 250014 Shandong,China;Jinan Municipal Hospital of Traditional Chinese Medicine,Jinan 250012 Shandong,China;Jinan Vocational College of Nursing,Jinan 250102 Shandong,China;The First Affiliated Hospital of Shandong First Medical University,,Jinan 250014 Shandong,China)

机构地区：[1]山东中医药大学,山东济南250014 [2]济南市中医医院,山东济南250012 [3]济南护理职业学院,山东济南250102 [4]山东第一医科大学第一附属医院,山东济南250014

出　　处：《中药新药与临床药理》2022年第12期1665-1672,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：济南市卫生健康委员会科技计划项目(2020-4-56)。

摘　　要：目的 利用网络药理学思路和实验研究探讨银杏叶治疗血栓闭塞性脉管炎的机制。方法 检索中药系统药理学数据库与分析平台获取银杏叶有效成分和作用靶点,检索基因卡片和人类在线孟德尔遗传平台获取血栓闭塞性脉管炎相关靶点,构建银杏叶干预血栓闭塞性脉管炎的“药物-成分-靶点-疾病”网络,利用Cytoscape软件对银杏叶干预血栓闭塞性脉管炎的关键靶点进行蛋白质相互作用分析。基于R语言“Bioconductor”数据包进行基因组百科全书信号通路富集分析。复制血栓闭塞性脉管炎大鼠模型,验证银杏叶治疗血栓闭塞性脉管炎的机制。结果 筛选获得27种银杏叶有效成分、186个银杏叶干预血栓闭塞性脉管炎的潜在靶点和肿瘤坏死因子(TNF)、白细胞介素17(IL-17)、缺氧诱导因子1(HIF-1)、Toll样受体(ILR)以及核转录因子κB(NF-κB)等信号通路。动物实验结果证明,银杏叶可显著下调血栓闭塞性脉管炎模型大鼠股动脉肿瘤坏死因子α(TNF-α)、核转录因子kappa B(NF-κB)、血管细胞黏附因子1(VCAM-1)、核因子kappa B抑制因子α(IκBα)的表达量(P<0.05),验证了网络药理学部分预测结果。结论 银杏叶可通过下调肿瘤坏死因子α、核转录因子kappa B、血管细胞黏附因子1、核因子kappa B抑制因子α的表达干预血栓闭塞性脉管炎。Objective To explore the mechanism of Ginkgo Folium intervening thromboangiitis obliterans by using network pharmacology and experimental research. Methods Traditional Chinese medicine systems pharmacology database and analysis platform was used to mine the active components of Ginkgo Folium and predict their targets.The target of thromboangiitis obliterans was screened out by GeneCards and online Mendelian inheritance in man databases. The "drug-component-target-disease" network of Ginkgo Folium intervening thromboangiitis obliterans was constructed. The protein interaction analysis of key targets for Ginkgo Folium intervening thromboangiitis obliterans was performed using Cytoscape software. The signal pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes was carried out based on R “Bioconductor” package. Rat models with thromboangiitis obliterans were replicated to verify the mechanism of Ginkgo Folium intervening thromboangiitis obliterans. Results Twenty-seven active components of Ginkgo Folium,186 potential targets of Ginkgo folium intervening thromboangiitis obliterans and signaling pathways,such as tumor necrosis factor(TNF),interleukin 17(IL-17),hypoxia-inducible factor 1(HIF-1),toll-like receptor(ILR)and nuclear factor kappa B(NF-κB)were screened. The results of animal experiments suggested that Ginkgo Folium could significantly downregulate the expression of tumor necrosis factor α(TNF-α),nuclear factor kappa B(NF-κB),vascular cell adhesion molecule-1(VCAM-1)and inhibitor α of nuclear factor kappa B(IκBα)(P<0.05)in the femoral artery of rat models with thromboangiitis obliterans,which verified partial prediction results of the network pharmacology. Conclusion Ginkgo Folium could downregulate the expression of TNF-α,NF-κB,VCAM-1 and IκBα in the treatment of thromboangiitis obliterans.

关 键 词：血栓闭塞性脉管炎 银杏叶 网络药理学 作用机制 肿瘤坏死因子α(TNF-α) 核转录因子kappaB(NF-κB) 

分 类 号：R285.5[医药卫生—中药学]