葛根汤治疗骨关节炎的网络药理学分析及动物实验验证  

Pueraria decoction in the treatment of osteoarthritis:network pharmacology analysis and animal model validation

作　　者：刘宝方 徐斌[1] 陈雷 Liu Baofang;Xu Bin;Chen Lei(Department of Orthopedics,the First Affiliated Hospital of Anhui Medical University,Hefei 230001,Anhui Province,China;Department of Burns and Plastic Surgery,the First Affiliated Hospital of Wannan Medical College,Wuhu 241000,Anhui Province,China)

机构地区：[1]安徽医科大学第一附属医院骨科,安徽省合肥市230001 [2]皖南医学院第一附属医院烧伤整形科,安徽省芜湖市241000

出　　处：《中国组织工程研究》2024年第2期193-199,共7页Chinese Journal of Tissue Engineering Research

基　　金：安徽省自然科学基金项目(1808085MH243),项目负责人:徐斌;芜湖市科技计划项目(2021jc2-4),项目负责人:陈雷。

摘　　要：背景:葛根汤是中医著名方剂,具有抗炎止痛的良好疗效,通过网络药理学分析葛根汤在骨关节炎中的作用机制,从而获得葛根汤的主要疗效成分。目的:通过网络药理学和动物实验验证葛根汤治疗骨关节炎的作用机制。方法:首先,通过中草药分析平台(TCMSP)筛选葛根汤的活性成分,并在GeneCards数据库收集骨关节炎的相关基因;其次,利用Cytoscape软件构建“活性成分-作用靶点-疾病”网络图,探索核心靶基因及分析基因表达差异,随后通过小鼠骨关节炎模型进行葛根汤主成分之一木犀草素疗效的实验验证;最后,对靶标基因进行京都基因百科全书(KEGG)和基因本体(GO)富集分析进一步探索相关机制。结果与结论:筛选出115种活性成分和147个相对应的靶标基因,KEGG和GO分析发现葛根汤可通过多种反应机制和代谢通路影响骨关节炎,筛选出6个核心表达差异基因和作用于这些基因的化合物,其中葛根汤的主要成分木犀草素在动物实验中可以较好地促进软骨修复,促进胶原蛋白Ⅱ的表达,抑制基质金属蛋白酶1、环氧合酶2的表达。结果表明,葛根汤中含多种活性成分通过氧化应激等作用机制和代谢通路阻止骨关节炎的进展。BACKGROUND:Pueraria decoction is a famous prescription of traditional Chinese medicine,which has good anti-inflammatory and analgesic effects.The mechanism of Pueraria decoction in osteoarthritis was analyzed using network pharmacology to obtain the main therapeutic components of Pueraria decoction.OBJECTIVE:To analyze the mechanism of Pueraria decoction in the treatment of osteoarthritis through network pharmacology and animal experiments.METHODS:First,the active ingredients of Pueraria decoction were screened through the Chinese Herbal Medicine Analysis platform(TCMSP)and the genes related to osteoarthritis were collected in the GeneCards database.Second,Cytoscape software was used to construct the“active ingredient-target-disease”network diagram,explore hub genes and analyze gene expression differences.Subsequently,the therapeutic effect of luteolin,one of the main components of Pueraria decoction,was verified in a mouse model of osteoarthritis.Finally,the Kyoto Encyclopedia of Genes and Genomes(KEGG)and the gene ontology(GO)enrichment analyses of the target genes were conducted to further explore the relevant mechanisms.RESULTS AND CONCLUSION:115 active ingredients and 147 target genes related to osteoarthritis were identified.GO and KEGG analyses found that Pueraria decoction could affect osteoarthritis through a variety of reaction mechanisms and metabolic pathways.Six hub genes and compounds acting on these genes were determined.Luteolin,the main component of Pueraria decoction,could better promote cartilage repair,accelerate the decrease of typy II collagen and inhibit the expression of matrix metalloproteinase 1 and cyclooxygenase 2 in animal experiments.To conclude,Pueraria decoction contains various active ingredients to prevent the progression of osteoarthritis through oxidative stress and metabolic pathways.

关 键 词：葛根汤 骨关节炎 差异表达基因 网络药理学 信号通路 炎症反应 靶点预测 木犀草素 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R684.3