祛浊化瘀方治疗痛风性关节炎的作用及机制研究  

Exploring Effect of Quzhuo Huayu Formula(祛浊化瘀方)on Gouty Arthritis

作　　者：李志岭 胡莎莎 谢静静[1,2] 贾二涛 张剑勇[1,2] LI Zhiling;HU Shasha;XIE Jingjing;JIA Ertao;ZHANG Jianyong(The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen 518000,Guangdong,China;Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518000,Guangdong,China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518000 [2]深圳市中医院,广东深圳518000

出　　处：《中华中医药学刊》2024年第7期125-129,I0013-I0021,共14页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82174290);深圳市科技计划项目(JCYJ20210324120405016)。

摘　　要：目的探索祛浊化瘀方治疗痛风性关节炎作用及机制。方法通过TCMSP、GeneCards、DisGeNET、MalaCards、DAVID6.7等数据库,筛选出祛浊化瘀方的核心成分及核心靶点。通过GEO数据库获得痛风性关节炎模型小鼠基因数据,筛选样本之间的差异表达基因,GO分析以及KEGG信号通路富集分析共同的差异基因。分析痛风性关节炎组与正常组当中免疫细胞浸润情况,比较差异相关性。与网络药理学信号通路结果进行对比验证,综合得到的结果以确定作用靶点,并通过动物实验验证。结果网络药理学发现白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)是与痛风性关节炎相关密切的核心靶点。基于GEO数据库的差异表达基因分析,白细胞迁移、趋化,产生细胞因子、中性粒细胞迁移在内的多个生物过程,经由NF-κB路径的TNF-α信号通路等多个炎症信号通路参与痛风性关节炎,与网络药理学所得结果基本一致。通过免疫细胞浸润分析发现固有免疫细胞如中性粒细胞、巨噬细胞是主要的参与痛风性关节炎炎症反应的免疫细胞类型。动物实验结果显示:祛浊化瘀方能够降低痛风性关节炎模型组织局部IL-1β、TNF-α、IL-6表达,减少中性粒细胞胞外诱捕网的形成。结论祛浊化瘀方可能通过多成分、多靶点和多通路抑制炎症反应防治痛风性关节炎。Objective To explore the effect and mechanism of Quzhuo Huayu Formula(祛浊化瘀方,QZHY)in the treatment of gouty arthritis.Methods Through TCMSP,GeneCards,DisGeNET,MalaCards,DAVID6.7 and other databases,the core components and core targets of QZHY were screened.The gene data of gouty arthritis model mice were obtained through the GEO database,and the differences among the expression genes in the samples were screened,and the common differential genes were analyzed by GO analysis and KEGG signaling pathway enrichment.The infiltration of immune cells in the gouty arthritis group and the control group was analyzed,and the difference was compared.The results of the network pharmacological signaling pathway were compared and verified,and the results obtained were synthesized to determine the target of action and verified by animal experiments.Results Network pharmacology has found that IL-1β,IL-6,TNF-αare core targets closely related to gouty arthritis.Based on the differential expression gene analysis of GEO database,multiple biological processes including leukocyte migration,chemotaxis,cytokine production,neutrophil migration and TNF-αsignaling pathway through the NF-κB pathway participated in gouty arthritis,which were basically consistent with the results obtained by network pharmacology.Through immune cell infiltration analysis,it is found that innate immune cells such as neutrophils and macrophages were the main immune cell types involved in gouty arthritis inflammatory response.The results of animal experiments showed that the method of QZHY could reduce the expressions of local IL-1β,TNF-αand IL-6 in gouty arthritis model tissues and reduce the formation of extracellular trapping nets(NETs)of neutrophils.Conclusion QZHY might improve gouty arthritis inflammation through multi-component,multi-target and multi-pathway.

关 键 词：祛浊化瘀方 网络药理学 痛风性关节炎 炎症反应 

分 类 号：R289.5[医药卫生—方剂学]