基于网络药理学的三仙汤治疗骨质疏松症作用机制研究  

Study on the mechanism of sanxian decoction treatment of osteoporosis based on network pharmacology

作　　者：戴梦竹 任路[1] 何信用 王群 徐宁阳 陈文娜[2] DAI Mengzhu;REN Lu;HE Xinyong;WANG Qun;XU Ningyang;CHEN Wenna(Liaoning University of Traditional Chinese Medicine, Graduate School, Shenyang 110847, China;School of Medical Laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China)

机构地区：[1]辽宁中医药大学研究生学院,辽宁沈阳110847 [2]辽宁中医药大学医学检验学院,辽宁沈阳110847

出　　处：《中国骨质疏松杂志》2021年第6期831-837,842,共8页Chinese Journal of Osteoporosis

基　　金：国家重点研发计划(2018YFC1704301)。

摘　　要：目的通过网络药理学方法探讨三仙汤干预骨质疏松症(OP)的有效成分、作用靶点及信号通路等,从而明确其作用机制。方法应用中药系统药理学数据库与分析平台(TCMSP)检索获得三仙汤中3味药物的化学成分,通过Uniprot数据库,将已筛选出的靶点名称进行标准化。通过Genecards、OMIM数据库检索骨质疏松症的相关靶基因。将药物靶点与疾病靶点取交集,筛选得到疾病-药物成分共同靶蛋白在String网站构建蛋白-蛋白相互作用(PPI)网络模型。在Cytoscape软件中绘制药物、疾病、靶基因网络图,并进行基因GO功能和KEGG通路富集分析,探讨三仙汤治疗骨质疏松症的作用机制。结果通过数据库筛选得到三仙汤的28种有效成分以及与骨质疏松症相关的靶点127个,其中蛋白激酶、白介素6、血管内皮生长因子等基因为PPI网络中的核心基因;GO富集分析显示靶点主要影响核受体活性、转录因子活性、类固醇激素受体活性、细胞因子受体结合、蛋白质异二聚活性、血红素结合等生物过程;以及影响AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化通路、IL-17信号通路、前列腺癌通路、肿瘤坏死因子信号通路、乙型肝炎等信号通路。结论三仙汤中的有效成分通过关键信号通路作用于核心基因,影响细胞分化、凋亡、炎症、氧化应激等多种生物学过程发挥抗骨质疏松的作用,为其后续研究提供了科学依据。Objective Based on the network pharmacology,to explore the target,main drug ingredients and signal pathway of Sanxian Decoction in the treatment of osteoporosis(OP).Methods The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)was applied to retrieve the chemical components of three drugs in sanxian decoction,and the names of screened targets were standardized through Uniprot database.Genecards and OMIM databases were used to retrieve the relevant target genes of osteoporosis.Drug targets were intersected with disease targets,and disease-drug component common target proteins were screened to construct a protein-protein interaction(PPI)network model on the String website.Network maps of drugs,diseases and target genes were drawn in Cytoscape software,and gene GO function and KEGG pathway enrichment were analyzed to explore the mechanism of sanxian decoction in the treatment of osteoporosis.Results 28 active ingredients and 127 targets related to osteoporosis of Sanxian Decoction were screened from the database,Among them,AKT1,IL6,VEGFA were the core genes in the PPI network;GO enrichment analysis showed that the target mainly affected the processes such as nuclear receptor activity,transcription factor activity,direct ligand regulated sequence-specific DNA binding,steroid hormone receptor activity,cytokine receptor binding,protein heterodimerization activity,heme binding,etc al.as well as advanced AGE-RAGE signaling pathway in diabetic complications,stress and atherosclerosis,IL-17 signaling pathway,Prostate cancer,TNF signaling pathway,Hepatitis B signaling pathway and other signaling pathways that affect the diabetic complications.Conclusion The active components in the Sanxian decoction act on the core genes through the key signal pathway,affect cell differentiation,apoptosis,inflammation,oxidative stress and other biological processes to play an anti-osteoporosis role,it provides scientific basis for its follow-up research.

关 键 词：中医中药 三仙汤 网络药理学 骨质疏松症 靶点预测 分子机制 信号通路 

分 类 号：R285.6[医药卫生—中药学] R589.5[医药卫生—中医学]