基于网络药理学探讨积雪草治疗病理性瘢痕的靶点和作用机制  

Study on the target and mechanism of Centella asiatica for treatment of pathological scars based on network pharmacology

作　　者：狄海波 张洪壮 侯世科 王振国 闫利 DI Haibo;ZHANG Hongzhuang;HOU Shike;WANG Zhenguo;YAN Li(Institute of Burns,Frostbite and Tissue Function Reconstruction,Featured Medical Center of Chinese People’s Armed Police Forces,Tianjin 300162,China)

机构地区：[1]武警特色医学中心烧伤冻伤及组织功能重建研究所,天津300162

出　　处：《浙江医学》2020年第23期2538-2543,共6页Zhejiang Medical Journal

基　　金：天津市科技计划项目(15ZXLCSY00040);武警后勤学院基础科研项目(WHJ201721)。

摘　　要：目的通过网络药理学方法,预测积雪草治疗病理性瘢痕(PS)的作用靶点并探讨其作用机制。方法通过TCMSP数据库筛选出积雪草的活性成分和药物靶点,在GeneCards(https://www.genecards.org/)数据库获取PS疾病靶点,对积雪草药物靶点和PS疾病靶点进行韦恩图分析,以共同靶点作为积雪草治疗PS的作用靶点。通过String网站构建蛋白质相互作用(PPI)网络,用Cytoscape3.7.1软件绘制PPI网络图,并筛选其关键蛋白模块及关键(Hub)基因;在DAVID数据库对关键模块的Hub基因进行基因本体论(GO)功能注释和KEGG通路富集分析。结果筛选出槲皮素和谷甾醇2个活性成分,155个药物靶点,4571个PS疾病靶点;取交集后得到130个积雪草治疗PS的作用靶点。经Cytoscape软件分析后,得到丝裂原活化蛋白激酶1(MAPK1)、IL-6、TNF、IL-10、基质金属蛋白酶9(MMP-9)、转化生长因子β1(TGF-β1)、血管内皮生长因子A(VEGFA)、IL-1B、表皮生长因子(EGF)、MMP-2、MMP-1等Hub基因,涉及TNF信号通路、MAPK信号通路、HIF-1信号通路等。结论积雪草可通过调控TNF信号通路、MAPK信号通路、HIF-1信号通路等,改善PS患者的炎症反应、缺氧状态及成纤维细胞增殖平衡,具有多中心、多靶点、多途径的作用特点。Objective To study the target of Centella asiatica for treatment of pathological scar(PS)and to explore its mechanism based on network pharmacology.Methods The active ingredients and drug targets of Centella asiatica were screened through the TCMSP database,and PS disease targets were obtained from the GeneCards(https://www.genecards.org/)database.Venn diagram analysis on Centella asiatica drug targets and PS disease targets was performed to identify the common targets of Centella asiatica in PS treatment.A protein-protein interaction(PPI)network was constructed through the String website,and Cytoscape 3.7.1 software was used to generate a PPI network diagram,and its key protein modules and Hub genes were screened.GO function annotations and KEGG pathway enrichment were performed for the Hub genes of key modules in the DAVID database.Results Two active ingredients,quercetin and sitosterol,155 drug targets,4571 PS disease targets were screened out.One hundred and thirty Centella asiatica therapeutic targets were obtained after the intersection.After analysis by Cytoscape software,the Hub genes were obtained,including mitogen-activated protein kinase 1(MAPK1),interleukin 6(IL-6),tumor necrosis factor(TNF),IL-10,matrix metallopeptidase 9(MMP-9),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor-α(VEGFA),IL-1B,epidermal growth factor(EGF),MMP2,MMP1,etc.The involved signal pathways included TNF signal pathway,MAPK signal pathway,HIF-1 signal pathway and so on.Conclusion The study indicates that Centella asiatica may improve the inflammation,hypoxia,and balance of fibroblast proliferation in PS patients by regulating the TNF signaling pathway,MAPK signaling pathway,and HIF-1 signaling pathway with the characteristics of multiple centers,multiple targets,and multiple pathways.

关 键 词：病理性瘢痕 网络药理学 积雪草 靶点 

分 类 号：R285[医药卫生—中药学]