摘要 摘 要：基于网络药理学探求当归四逆汤作用于腰椎间盘突出症的作用机理。系统检索中药系统药理学技术平台（TCMSP）、中药潜在靶点数据库（TCM-PTD）获取当归四逆汤药物的有效活性成分45个，作用靶点132个，并将得到的靶点与通用蛋白数据库（Uniprot）中载入的基因名称简称进行匹配。通过检索人类基因数据库（GeneCards）和孟德尔疾病基因数据库（OMIM）来获取腰椎间盘突出症的作用靶点，汇入表格并去除重复靶点之后，共得到有效靶点379个。使用 ClusterProfiler R编程软件绘制Venn图，获取药物和疾病共同作用的靶点25个。利用Cytoscape Version 3.6.1软件，构建当归四逆汤活性成分-药物疾病共同作用靶蛋白网络。将药物疾病共同作用靶点导入功能性蛋白关联网络平台（STRING），获取蛋白互作网络，并使用Cytoscape Version 3.6.1软件对蛋白互作网络图进行拓扑分析和注释分析，得到核心靶点AKT1、PTGS2、MAPK1、STAT3、MAPK8、JUN、CASP3、MAPK14等。使用ClusterProfiler R 软件对疾病药物公共作用靶点进行基因本体论（GO）富集分析和京都基因与基因组百科全书数据库（KEGG）通路富集分析，并用Cytoscape Version 3.6.1绘制靶点-通路网络图，得到当归四逆汤的有效活性成分paeoniflorin、beta-sitosterol、kaempferol、(+)-catechin、stigmasterol、formononetin、licochalcone a、sesamin以及关键作用靶点IL6、AKT1、PTGS2、MAPK1、STAT3、MAPK8、JUN、CASP3、MAPK14、IL10等，并发现关键作用靶点主要通过丝裂原活化蛋白激酶（MAPK）活性、蛋白质丝氨酸/苏氨酸/酪氨酸激酶活性、血红素结合、磷酸酶结合、氧化还原酶活性、FMN结合、内肽酶活性、激素结合等功能，涉及 HIF-1、FoxO、NF-κB、MAPK、p35等信号通路治疗腰椎间盘突出症。该文揭示了当归四逆汤从多成分、多靶点、多通路的角度治疗腰椎间盘突出症的作用机制，为新药开发及临床应用提供了依据与新的思路。
关键词：当归四逆汤；腰椎间盘突出症；网络药理学；靶点；分子对接
中图分类号：R917 文献标志码：ADOI：10.3969/j.issn.1007-7146.2021.03.006
Abstract：Abstract: Based on network pharmacology, the mechanism of Danggui Sini Decoction on lumbar disc herniation is explored. We systematically searched the Chinese Medicine System Pharmacology Technology Platform (TCMSP) and the Chinese Medicine Potential Target Database (TCM-PTD) to obtain 45 active ingredients and 132 targets of Danggui Sini Decoction, and compared the obtained targets with the Uniprot database. The abbreviation of the loaded gene name was matched. By searching the Human Gene Database (GeneCards) and Mendelian Disease Gene Database (OMIM) disease target database, a total of 379 target of lumbar intervertebral disc herniation was obtained, after importing the table and removing the duplicate target. ClusterProfiler R programming software was used to draw a Venn diagram to obtain 25 targets for the joint action of drugs and diseases. Cytoscape Version 3.6.1 software was used to construct a network of target proteins of the active ingredient of Danggui Sini Decoction-drug disease. The drug-disease co-action target was imported into the functional protein association network platform which is search Tool for Recurring Instances of Neighbouring Genes, STRING, the protein interaction network was obtained, and Cytoscape Version 3.6.1 was used for the protein interaction network topological analysis and annotation analysis, and the work are performed on the graph to obtain core targets AKT1, PTGS2, MAPK1, STAT3, MAPK8, JUN, CASP3, MAPK14, etc. ClusterProfiler R software was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on the public action targets of disease drugs, and Cytoscape Version 3.6.1 was used to draw the target-pathway network diagram. Paeoniflorin, beta-sitosterol, kaempferol, (+)-catechin, stigmasterol, formononetin and licochalcone were obtained from the effective active ingredients of Danggui Sini Decoction and the key action targets, such as IL6, AKT1, PTGS2, MAPK1, STAT3, MAPK8, JUN, CASP3, MAPK14, IL10, etc. It is found that Danggui Sini Decoction mainly showed MAP kinase activity and protein serine threonine tyrosine kinase activity, heme binding, phosphatase binding, oxidoreductase activity, FMN binding, endopeptidase activity, hormone binding and other functions, involving HIF-1, FoxO, NF-κB, MAPK, signal pathways such as p35 treat lumbar disc herniation. This article reveals the mechanism of action of Danggui Sini Decoction in treating lumbar disc herniation from the perspective of multiple components, multiple targets, and multiple pathways, providing basis and new ideas for new drug development and clinical application.
Key words: Danggui Sini Decoction; lumbar disc herniation; network pharmacology; target; molecular docking
（Acta Laser Biology Sinica, 2021, 30(3): 236-249）
引用本文:
张水冰，李 颖，赵思怡，黄 帆，海那尔·乌拉孜巴依，丘明旺，方婉仪，姚 琳，张茂祥. 基于蛋白互作和关键作用靶点的网络药理学研究当归四逆汤治疗腰椎间盘突出症的作用机理[J]. 激光生物学报, 2021, 30(3): 236-249.
ZHANG Shuibing, LI Ying, ZHAO Siyi, HUANG Fan, WULAZIBAYI Hainaer, QIU Mingwang, FANG?Wanyi, YAO Lin, ZHANG Maoxiang. A Network Pharmacology Analysis of the Traditional Chinese Danggui Sini Decoction in Patients with Lumbar Disc Herniation. journal1, 2021, 30(3): 236-249.
