基于网络药理学和分子对接探讨干姜附子汤治疗慢性肾功能衰竭的作用机制  

A study on the mechanism of the Ganjiang Fuzi decoction on CRF based on network pharmacology and molecular docking

作　　者：穆苏宁 于卓 MU Suning

机构地区：[1]黑龙江省中医药科学院,黑龙江哈尔滨150036

出　　处：《中医临床研究》2024年第19期19-26,共8页Clinical Journal Of Chinese Medicine

摘　　要：目的:运用网络药理学方法探讨干姜附子汤治疗慢性肾功能衰竭的作用机制,旨在为其临床应用及基础研究提供依据。方法:通过HERB数据库和中药系统药理学数据库与分析平台(TCMSP)查找干姜附子汤药物的主要活性成分,使用SwissTargetPrediction平台进行靶点预测。检索GeneCards、DisGeNET及OMIM数据库,获取慢性肾功能衰竭的疾病靶点,并获取交集靶点。使用STRING 11.0平台构建蛋白质-蛋白质相互作用关系,使用CytoScape 3.9.1软件构建蛋白质-蛋白质相互作用网络,筛选核心靶点。通过Metascape数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。运用AutoDock软件将干姜附子汤主要活性成分与慢性肾功能衰竭核心靶点进行分子对接。结果:共获得干姜附子汤有效成分84种,1 810个慢性肾功能衰竭相关基因。根据度值可知主要有效成分为8-甲氧基黄酮、水黄皮素、厚朴酚、脱氢皮质酮等;度值居前6位的靶点为SRC原癌基因(SRC Proto-Oncogene,SRC)、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、白细胞介素(Interleukin,IL)-6和肿瘤坏死因子(Tumor Necrosis Factor,TNF)。GO富集分析得到1 106个结果,其中包括生物过程854个条目、细胞组分89个条目、分子功能163个条目;KEGG富集分析得到170条通路。分子对接结果证实,有效活性成分均能与核心靶点较好结合。结论:干姜附子汤干预慢性肾功能衰竭可能与SRC、STAT3、AKT1、EGFR、IL-6、TNF等靶点有关,推测磷脂酰肌醇3激酶-蛋白激酶B(Phosphatidylinositol 3 Kinase-Akt,PI3K-Akt)、脂质和粥样硬化、钙离子、脂肪细胞因子及过氧化物酶体增殖物激活受体(Peroxisome Proliferator Activated Receptor,PPAR)等信号通路为干姜附子汤抗肾纤�Objective:To explore the mechanism of the Ganjiang Fuzi decoction(干姜附子汤)in the treatment of CRF by Onetwork pharmacology,so as to provide evidence for its clinical application and basic research.Methods:The main active ingredients of the Ganjiang Fuzi decoction were searched by HERB database and TCMSP,and the target prediction was carried out by SwissTargetPrediction platform.The GeneCards,DisGeNET and OMIM database were searched to obtain the disease targets of CRF and the intersection genes.STRING 11.0 platform was used to construct protein-protein interaction(PPI)relationship,and CytoScape 3.9.1 software was used to construct PPI network and screen core targets.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed through the Metascape database.The main active components of the Ganjiang Fuzi decoction was docked with CRF core target using AutoDock software.Results:A total of 84 active ingredients and 1810 genes related to CRF were obtained.According to the degree value,the main effective components were 8-methoxyflavone,karanji,magnolol,dehydrocorticosterone,etc.,the top 6 targets were SRC,STAT3,AKT1,EGFR,IL-6,TNF.GO enrichment analysis obtained 1106 results,including 854 items of biological process,89 items of cell composition,and 163 items of molecular function.KEGG enrichment analysis obtained 170 pathways.The results of molecular docking confirmed that all the active components could bind well with the core target.Conclusion:The intervention of the Ganjiang Fuzi decoction on CRF may be related to SRC,STAT3,AKT1,EGFR,IL-6,TNF and other targets.It is speculated that PI3K-Akt,lipid and atherosclerosis,calcium ion,adipocyte factor and PPAR signaling pathways are the potential pathways for the Ganjiang Fuzi decoction to exert anti-renal fibrosis.It provides a new idea and method for further study on the mechanism of the Ganjiang Fuzi decoction in the intervention of CRF.

关 键 词：网络药理学 干姜附子汤 慢性肾功能衰竭 

分 类 号：R692.5[医药卫生—泌尿科学]