基于网络药理学的左归丸治疗骨质疏松作用机制探讨  

Study on the mechanism of Zuogui pill in treating osteoporosis based on network pharmacology

作　　者：李晶[1] 吴立蔚 许杨[1,2] 肖承祥 周波 Jing Li;LiweiWu;Yang Xu;Chengxiang Xiao;Bo Zhou(Guangxi Medical University,Nanning 530021,China;The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Southern Theater Air Force Hospital,Guangzhou 510000,China)

机构地区：[1]广西医科大学,南宁530021 [2]广西医科大学第一附属医院,南宁530021 [3]南部战区空军医院,广州510000

出　　处：《广西医科大学学报》2021年第12期2199-2207,共9页Journal of Guangxi Medical University

摘　　要：目的:采用网络药理学方法探究左归丸对治疗骨质疏松的有效活性成分、作用靶点和潜在分子机制。方法:利用TCMSP数据库预测左归丸活性成分,筛选潜在的活性成分及作用靶点,在GeneCards数据库检索出骨质疏松相关的疾病靶点基因,通过Drugbank和Uniprot数据库筛选后,得到左归丸—骨质疏松疾病交集基因。采用Cytoscape3.8.2软件构建药物成分—疾病网络图,利用交集基因构建蛋白质互作网络,并获得左归丸治疗骨质疏松的核心网络和核心靶点基因,利用MCODE和Metascape数据库分析核心靶点基因,通过Metascape数据库对相关靶点进行GO生物富集分析和KEGG通路分析。最后,利用体外细胞实验进一步验证。结果:预测得到左归丸245个有效靶点和骨质疏松相关的疾病靶点4576个,两者共同靶点有171个。有效成分中度值较高的是槲皮素、山奈酚、异鼠李素、β-谷甾醇、24-亚甲基苯酚,PPI网络中核心基因是APP、NTRK1、EGFR、CUL3、HSP90AA1。GO富集分析涉及DNA结合转录因子结合、RNA聚合酶Ⅱ特异性DNA结合转录因子结合、核受体活性;KEGG通路富集分析结果显示,共同靶点可通过AGE-RAGE信号通路、TNF信号通路、IL-17信号通路、HIF-1信号通路等多条信号通路发挥作用。体外细胞实验表明左归丸可能抑制破骨细胞的形成。结论:左归丸可能通过抑制破骨细胞生成相关作用机制发挥预防和治疗骨质疏松症,为后续基础实验研究提供新的思考路线及方法。Objective:To explore the effective active ingredients,targets and potential molecular mechanisms of Zuogui pill in the treatment of osteoporosis by means of network pharmacology.Methods:Using the TCMSP database to predict the active ingredients of Zuogui pill,and to screen out the potential active ingredients and targets.The disease target genes related to osteoporosis were retrieved from the GeneCards database.After screening through the Drugbank and Uniprot databases,the Zuogui pill-osteoporosis disease intersection genes were finally obtained.Cytoscape 3.8.2 software was used to construct a drug component-disease network diagram,and the intersection genes were used to construct a protein interaction network,and the core network and core target genes of Zuogui pill treatment for osteoporosis were obtained,and the core target genes were analyzed by using MCODE and Metascape databases.GO bio-enrichment analysis and KEGG pathway analysis were performed on the relevant targets through the Metascape database.Finally,cell experiments were used to further verify the effects of Zuogui pill on osteoclasts in vitro.Re⁃sults:A total of 245 effective targets of Zuogui Pill and 4,576 targets of osteoporosis-related diseases are predicted,and there are 171 common targets.The active ingredients with higher moderate values are quercetin,kaempferol,isorhamnetin,β-sitosterol,and 24-methylenephenol.The core genes in the PPI network are APP,NTRK1,EGFR,CUL3,and HSP90AA1.GO enrichment analysis involves DNA binding transcription factor binding,RNA polymerase II specific DNA binding transcription factor binding and nuclear receptor activity;KEGG pathway enrichment analysis results show that the common targets can pass through the AGE-RAGE signaling pathway,TNF signaling pathway,IL-17 signal pathway,HIF-1 signal pathway and many other signal pathways.The cell experiments show that Zuogui pill could inhibit the formation of osteoclasts In vitro.Conclusion:Zuogui pill may play a role in the prevention and treatment of osteoporosis by

关 键 词：左归丸 骨质疏松 网络药理学 

分 类 号：R285.5[医药卫生—中药学]