基于网络药理学探讨加减木防己汤抗大鼠痛风性关节炎机制研究  

Research on Modified Mufangji Decoction(加减木防己汤) on Gout Arthritis in Rats and Its Mechanism Study Based on Network Pharmacology

作　　者：杜佳蓉 李楠[1] 吴威 张会永[1,3] 宋芷琪 李威莹 杨关林[1] DU Jiarong;LI Nan;WU Wei;ZHANG Huiyong;SONG Zhiqi;LI Weiying;YANG Guanlin(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Zhuhai College of Science and Technology,Zhuhai 519041,Guangdong,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]珠海科技学院,广东珠海519041 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《辽宁中医药大学学报》2022年第11期30-39,共10页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家科技部重大专项重大新药创制项目(2009ZX09502-029);辽宁省科技厅项目(20010ZX09401-304);岐黄学者-国家中医药领军人才支持计划(国中医药人教发[2018]12号)。

摘　　要：目的 运用经典方剂加减木防己汤对大鼠痛风性关节炎模型进行初步实验验证,并借助网络药理学技术预测并筛选其主要活性成分及潜在靶点,探讨其抗痛风性关节炎的作用机制。方法 从大鼠踝关节周长、活动能力、疼痛及病理组织等方面观察加减木防己汤的疗效。运用中药系统药理学技术平台(TCMSP)和中药综合数据库(TCMID)筛选加减木防己汤中药物的活性成分和靶点,通过Uniprot数据库查询靶点对应基因,运用Cytoscape3.8.0构建“药物-活性成分-靶点”网络图;通过Genecards、DisGeNET、DrugBank、OMIM数据库查询痛风性关节炎相关靶点基因;构建韦恩图,得到加减木防己汤治疗痛风性关节炎的作用靶点;并运用String数据库构建靶点蛋白互作(PPI)网络,运用Metascape数据库对共同靶点进行GO功能富集分析和KEGG通路富集分析。结果 实验发现,加减木防己汤能减轻大鼠关节肿胀高峰、改善关节活动能力、减轻疼痛和炎症浸润。从加减木防己汤中筛选得到相关活性成分59个,作用于151个靶点,主要活性成分有β-谷甾醇、豆甾醇、异甘草素、左旋千金藤啶碱、光甘草定等,获得具有治疗痛风性关节炎功能的关键靶标27个,涉及INS、ALB、PTGS2、EDN1、FOS、PPARG、CRP、RELA等。GO功能富集分析显示其干预炎症反应的调节、参与炎症反应的分子介质的产生、活性氧代谢、MAPK级联正调控等生物过程,KEGG通路分析显示cAMP信号通路、PPAR信号通路、Apelin信号通路、AMPK信号通路可能与加减木防己汤治疗痛风性关节炎的作用机制有关。结论 加减木防己汤对于大鼠痛风性关节炎有疗效,可能通过抑制炎症及相关炎症通路而抗痛风,为临床应用和实验研究提供参考。此外,加减木防己汤对于痛风合并心血管疾病和糖尿病并发症存在潜在治疗作用。Objective Using Modified Mufangji Decoction(加减木防己汤)to experiment on the rat gout arthritis model preliminarily,and using network pharmacology technology to predict and screen the main active ingredients and potential targets of it,to explore the mechanism of action in the treatment of gouty arthritis.Methods The effect of Modified Mufangji Decoction was observed from rats’ankle circumference,mobility,pain and pathological tissue.The active ingredients and action targets of the drugs composed of Modified Mufangji Decoction were screened by TCMSP and TCMID.The corresponding genes of the targets were searched through Uniprot database.Cytoscape3.8.0 was used to construct the network diagram of“drug-active ingredients-target”.Searching target genes related to gouty arthritis by GeneCards,DisgenET,DRUG BANK and OMIM databases.Targets of the treatment of gouty arthritis by Modified Mufangji Decoction were obtained by constructing Venn diagram.The target protein interaction(PPI)network was constructed using String database,and the gene ontology(GO)function enrichment analysis and KEGG pathway enrichment analysis were performed on the common targets using Metascape database to predict the mechanism of action.Results It was found that Modified Mufangji Decoction could reduce the peak of joint swelling,improve joint mobility,relieve pain and inflammatory infiltration.Fiftynine active components were screened from Modified Mufangji Decoction,which acted on 151 targets.The main active components includedβ-sitosterol,stigmastol,isoglycyrrhiza,levosorpidine,glabridine,etc.,and 27 key targets with therapeutic function of gouty arthritis were obtained.Involved in INS,ALB,PTGS2,EDN1,FOS,PPARG,CRP,RelA,etc.GO functional enrichment analysis showed that it interferes with the regulation of inflammatory response,production of molecular mediators involved in inflammatory response,metabolism of reactive oxygen species,positive regulation of MAPK cascade and other biological processes.KEGG pathway analysis showed that

关 键 词：网络药理学 痛风性关节炎 加减木防己汤 炎症信号通路 

分 类 号：R285.5[医药卫生—中药学]