摘要
目的从“疾病-分期-证型-方药”关联网络切入,探索羌活胜湿汤治疗类风湿关节炎(RA)急性期(风湿痹阻证)的作用机制。方法依托GEO数据库挖掘RA疾病基因,利用HPO、DisGeNET数据库收集RA急性期(风湿痹阻证)基因,通过TCMSP数据库检索羌活胜湿汤活性较高的化合物及靶点,并取上述基因集的交集为“病-期-证-方”关联网络基因。将得到的交集基因上传至STRING数据库构建PPI网络,利用Cytoscape软件构建生物分子网络,计算拓扑特征值(介度值、连接度、紧密度)并筛选关键靶点、核心节点。最后采用DAVID分析平台对基因进行生物功能注释、富集分析。结果筛选得到RA疾病基因5700个、急性期风湿痹阻证基因1323个、羌活胜湿汤活性成分靶点249个“、病-期-证-方”共同靶点48个、关键靶点21个、核心节点5个(IL-6、TNF、VEGFA、CASP3、PPARG)。“病-期-证-方”共同靶点在肢体沉重、滑膜炎、关节肿胀、关节疼痛、头痛、ESR增高、CRP增高、汗出、关节屈伸不利等证候基因中所占的比例分别为6.63%、5.86%、5.56%、4.81%、3.99%、3.57%、3.08%、2.23%、1.85%。GO富集分析的生物过程包括对药物的反应、正向调控细胞凋亡过程;细胞组分主要作用于细胞外间隙、内质网管腔;分子功能主要涵盖酶结合、蛋白质结合等。KEGG通路富集结果主要与调节血管生成、血液循环相关;调节骨、肌肉代谢失调相关;调节免疫、炎症系统失衡相关;滑膜血管翳生成及炎症相关通路。结论羌活胜湿汤治疗RA急性期(风湿痹阻证)具有多成分、多靶点、多通路的特点,与目前RA急性期的发病机制相符合。
Objective:To explore the mechanisms of Qianghuo Shengshi Decoction intervention in treating acute active rheumatoid arthritis(RA)with syndrome of wind-dampness blockage based on a"disease-stage-syndromeformula"'association network analysis.Methods:GEO database was searched to obtain the gene chip of RA.HPO and DisGeNET databases were searched to obtain the gene set of acute active RA of syndrome of wind-dampness blockage.The effective chemical components and related targets of Qianghuo Shengshi Decoction were found in TCMSP.The intersection of the above gene sets was taken as the"disease-stage-syndrome-formula"association network genes.The intersection genes were uploaded to the STRING database to build a PPI network.Cytoscape software was used to build a biomolecular network,calculate the topological eigenvalues(degree,betweenness centrality,and closeness centrality),screen the key targets and core nodes.Finally,Gene Ontology(CO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were conducted by DAVID analysis plaform.Results:In total,there were 5700 RA disease genes,1323 genes for acute active RA of syndrome of wind-dampness,249 targets for Qianghuo Shengshi Decoction,48 common targets of"disease-stage-syndrome-formula"association network,21 key targets and 5 core nodes(IL-6,TNF,VECFA,CASP3,PPARG).The common target of"disease-stage-syndrome-formula"accounted for 6.63%,5.86%,5.56%,4.81%,3.99%,3.57%,3.08%,2.23%and 1.85%in the heavy limbs,synovitis,joint swelling,arthralgia,headache,elevated erythrocyte sedimentation rate,elevated C-reactive protein concentration,sweating,and adverse joint flexion and extension,respectively.The biological process of GO enrichment analysis included response to drug and positive regulation of apoptotic process.The cellular component included extracellular space and endoplasmic reticulum lumen.The molecular function included enzyme binding and protein binding.KECG pathway enrichment results included blood circulation,regulation of bone and muscle metabolism,regulation of immune and inflammatory systems,synovial pannus generation and inflammation-related pathways.Conclusion:The treatment of acute active RA of syndrome of wind-dampness blockage by Qianghuo Shengshi Decoction has the characteristics of multi components,multiple targets and multiple pathways,which is consistent with the current pathogenesis of acute active RA.
作者
李文龙
梅沉成
谭彪
张兵
林娜
马显志
陈卫衡
Li Wenlong;Mei Chencheng;Tan Biao;Zhang Bing;Lin Na;Ma Xianzhi;Chen Weiheng(Beijing Hepingli Hospial,Beijing 100013,China)
出处
《中国中医急症》
2023年第5期760-764,共5页
Journal of Emergency in Traditional Chinese Medicine
基金
国家自然科学基金重点项目(81630107)
北京中医药大学高层次人才科研启动项目(2021-XJ-KYQD-001)。
关键词
类风湿关节炎
急性期
羌活胜湿汤
风湿痹阻证
“病-期-证-方”关联网络
作用机制
Rheumatoid arthritis
Acute stage
Qianghuo Shengshi Decoction
Syndrome of wind-dampness blockage
"Disease-stage-syndrome-formula"association network analysis
Pharmacological mechanism
