NLRP3介导的六君子汤治疗慢性萎缩性胃炎及炎癌转化的作用机制分析  

Mechanism Analysis on Liujunzi Decoction Mediated by NLRP3 in Treating Chronic Atrophic Gastritis and Inflammation-Cancer Transformation

作　　者：孙庆生 黄彭 李希 张姗 张照兰[6] SUN Qingsheng;HUANG Peng;LI Xi;ZHANG Shan;ZHANG Zhaolan(Zhengzhou Traditional Chinese Medicine Hospital,Zhengzhou Henan China 450000;The First Affiliated Hospital to Dalian Medical University,Dalian Liaoning China 116011;The People′s Hospital of Suixian County,Shangqiu Henan China 476900;The People′s Hospital of Weifang City,Weifang Shandong China 261000;The People′s Hospital of Yucheng County,Shangqiu Henan China 476300;The First Affiliated Hospital to Henan University of Chinese Medicine,Zhengzhou Henan China 450000)

机构地区：[1]郑州市中医院,河南郑州450000 [2]大连医科大学附属第一医院,辽宁大连116011 [3]睢县人民医院,河南睢县476900 [4]潍坊市人民医院,山东潍坊261000 [5]虞城县人民医院,河南虞城476300 [6]河南中医药大学第一附属医院,河南郑州450000

出　　处：《中医学报》2023年第11期2434-2442,共9页Acta Chinese Medicine

基　　金：辽宁省自然资金指导计划项目(2019-ZD-0914)。

摘　　要：目的:基于核苷酸结合寡聚化结构域样受体蛋白3(Nod-like receptor protein 3,NLRP3)相关靶点研究六君子汤治疗慢性萎缩性胃炎及炎癌转化的作用机制。方法:通过CTD、STRING和STITCH数据库预测NLRP3相关靶点。从TCMSP筛选六君子汤组方中药的活性成分,并利用DrugBank和Swiss Target Prediction预测成分相关靶点。通过Cytoscape软件获取活性成分相关靶点和NLRP3相关靶点的交集,构建“中药-活性成分-交集靶点-NLRP3”网络图,拓扑分析筛选核心活性成分。从DisGeNET数据库、GeneCards数据库、CTD数据库、药物靶标数据库(therapeutic target database,TTD)检索疾病相关靶点。通过Cytoscape 3.2.1软件Merge功能取慢性萎缩性胃炎相关靶点和NLRP3相关靶点的交集,并构建“慢性萎缩性胃炎-NLRP3”网络图。将“中药-活性成分-交集靶点-NLRP3”网络图和“慢性萎缩性胃炎-NLRP3”网络图相交,获取潜在靶点,通过STRING数据库获取潜在靶点相互作用网络,并利用Cytoscape软件将结果进行可视化,获得蛋白质相互作用(protein-protein interaction,PPI)网络,通过网络拓扑分析揭示关键靶点,并与核心活性成分进行分子对接。通过DAVID对靶点进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and gnomes,KEGG)通路富集分析。结果:以“NRLP3”为关键词获得270靶点。从TCMSP数据库得到六君子汤组方中药152个活性成分,从DrugBank和Swiss Target Prediction预测得到181个成分相关靶点。“中药-活性成分-交集靶点-NLRP3”网络拓扑分析发现山柰酚和柚皮素可能为核心活性成分。将“中药-活性成分-交集靶点-NLRP3”网络图和“慢性萎缩性胃炎-NLRP3”网络图相交,获取11个潜在靶点。PPI网络分析显示,JUN、PPARG、AKT1和TNF等靶点可能为关键靶点。KEGG富集分析得到23条信号通路,其中TNF信号通路和MAPK等信号通路可能发挥重要作用。分子对接结果显示,核心靶点MObjective:To study the mechanism of Liu Junzi Decoction in treating chronic atrophic gastritis and inflammation-cancer transformation based on related targets of NOD-LIKER domain-like receptor protein 3(NLRP3).Methods:the related targets of NLRP3 were predicted by CTD,STRING and STITCH databases The active components of Liujunzi decoction were screened from TCMSP,and the related targets of the components were predicted by DrugBank and Swiss Target Prediction.The intersection of active ingredient-related targets and NLRP3-related targets was obtained by Cytoscape software,and the network diagram of"Chinese medicine-active ingredient-intersection target-NLRP3"was constructed,and the core active ingredients were screened by topological analysis.Disease-related targets were retrieved from DisGeNET database,GeneCards database,CTD database and therapeutic target database(TTD).The intersection of chronic atrophic gastritis-related targets and NLRP3-related targets was obtained by the Merge function of Cytoscape 3.2.1 software,and the network diagram of"Chronic atrophic gastritis-NLRP3"was constructed.The network diagram of"Traditional Chinese Medicine-Component-Target-NLRP3"and the network diagram of"Chronic Atrophic Gastritis-NLRP3 Mediated Disease Target"are intersected to obtain the potential target.The interaction network of the potential target is obtained through STRING data,and the results are visualized by Cytoscape to obtain the protein interaction(PPI)network.The key target is revealed through network topology analysis,and it is connected with the core active components.By DAVID,the pathway enrichment of Kyoto encyclopedia of genes and genomes(KEGG)was analyzed.Results:270 targets were obtained with"NRLP3"as the keyword.152 active components of Liujunzi decoction were obtained from TCMSP database,and 181 targets related to components were predicted from DrugBank and Swiss Target Prediction.Topological analysis of"Chinese medicine-component-target-NLRP3"network found that kaempferol and naringin may be the core

关 键 词：慢性萎缩性胃炎 炎癌转化 NLRP3 六君子汤 网络药理学 

分 类 号：R285[医药卫生—中药学]