摘　要 ：通过网络药理学与分子对接的方法研究防己黄芪汤治疗小儿肾病综合征（NS）的作用机制。系统检索TCMSP平台获取防己黄芪汤的有效活性成分78个、作用靶点206个，并依据Uniprot已载入的基因名称规范靶点的名称。通过检索OMIM、DisGenet数据库获取小儿肾病综合征的作用靶点，对收集到的疾病靶点进行去重整理并通过Uniprot数据库进行规范后，共收集到疾病靶点1 754个。通过韦恩在线平台绘制韦恩图，获取药物和疾病的共同靶点48个。通过Cytoscape软件绘制防己黄芪汤活性成分-药物-疾病共同作用靶蛋白网络，依据自由度值选取关键活性成分槲皮素、7-O-甲基-异微凸剑叶莎醇、山奈酚、美迪紫檀素、4′，-甲氧基光甘草定。将药物疾病共有靶点导入String平台，获取蛋白互作网络，并通过Cytoscape软件对蛋白互作网络进行拓扑分析和网络子模块分析，得到核心靶点AKT1、MYC、TP53。通过Metascape平台对公共作用靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，发现主要涉及到的生物过程有循环系统、细胞应激、生长调节、蛋白质丝氨酸/苏氨酸激酶活性的调节、白细胞分化等，与小儿肾病综合征有关的通路主要有MAPK信号通路和PI3K-Akt信号通路。通过AUTODOCK软件对关键靶点和关键成分进行分子对接，结果均小于-5.0 kcal/mol。经过分析发现，防己黄芪汤对于小儿NS的治疗主要依赖于MAPK和PI3K-Akt两条信号通路，并且通过槲皮素、7-O-甲基-异微凸剑叶莎醇、山奈酚、美迪紫檀素、4′，-甲氧基光甘草定等活性成分作用于MYC、AKT1靶蛋白，同时需要循环系统、细胞应激、生长调节、蛋白质丝氨酸/苏氨酸激酶活性的调节、白细胞分化等多种生物过程的参与来实现多成分、多靶点、多层次、多途径复杂的综合调控。该研究为防己黄芪汤进一步的研究和临床应用提供了参考依据。
关键词：防己黄芪汤；小儿肾病综合征；网络药理学；分子对接；作用机制
中图分类号：R272                             文献标志码：A                      DOI：10.3969/j.issn.1007-7146.2021.06.012

Abstract: Exploring the mechanism of Fangji Huangqi Decoction in the treatment of children with nephrotic syndrome by means of network pharmacology and molecular docking. We systematically searched TCMSP platform to obtain 78 active ingredients and 132 targets of Fangji Huangqi Decoction, and standardized the target name according to the gene name loaded by UniProt database. By searching the OMIM and DisGenet databases, a total of 1 754 targets of pediatric nephrotic syndrome were obtained, after removing the duplicate targets and standardizing target name according to the Uniprot database. Drawing a Venn diagram through Venn online platform was conducted to obtain 48 targets for the common parts of drugs and diseases. Cytoscape software was used to construct a network of target proteins of the active ingredient of Fangji Huangqi Decoction-drug disease. Quercetin, kaempferol, medicarpin, 7-O-methylisomucronulatol, 2-［(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano ［6,5-f］ chromen-3-yl］-5-methoxyphenol were selected as the key active ingredients according to the degree of the network. The drug-disease common targets were imported into the String platform, the protein interaction network was obtained. Cytoscape was used for the protein interaction network topological analysis and sub-module analysis. Through this work, the core targets AKT1, MYC, and TP53 were obtained. The metascape platform was used to perform GO biological processes and KEGG enrichment pathway analysis on the common targets of disease drugs, it was found that the GO biological process is mainly related to blood system, cell stress, regulation of growth, regulation of protein serine/threonine kinase activity,  leukocyte differentiation. The result of KEGG pathway is mainly related to the MAKP signaling pathway and the PI3K-Akt signaling pathway. The molecular docking of key targets and key components was carried out by AUTODOCK software, the results were all less than -5.0 kcal/mol. After the analysis, it was found that Fangji Huangqi Decoction for the treatment of pediatric nephrotic syndrome mainly relies on the two signal pathways of MAPK and PI3K-Akt, and acts on MYC, AKT1 target proteins through quercetin, kaempferol, mediterrantol, 7-O-methylisomucronulatol, 2-［(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano ［6,5-f］ chromen-3-yl］-5-methoxyphenoand other active ingredients. Meanwhile, it requires the participation of various biological processes, such as the circulatory system, cell stress, growth regulation, protein serine/threonine kinase activity regulation, leukocyte differentiation, etc, to achieve complex comprehensive regulation with multiple components, multiple targets, multiple levels, and multiple pathways. It provides a reference for the further research and clinical application of Fangji Huangqi Decoction.
Key words: Fangji Huangqi Decoction; pediatric nephrotic syndrome; network pharmacology; molecular docking; mechanism
（Acta Laser Biology Sinica, 2021, 30(6): 565-576）