基于网络药理学探讨芪术颗粒治疗糖尿病肾病的作用机制  

Network Pharmacology Approach to Explore Mechanisms of Qizhu Granules for Treatment of Diabetic Nephropathy

作　　者：蔺亚东 高文静 侯敏 王攀 雷蕾[2] 任钧国[1] LIN Ya-dong;GAO Wen-jing;HOU Min;WANG Pan;LEI Lei;REN Jun-guo(Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Institute of Information on Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院西苑医院基础医学研究所,北京100091 [2]中国中医科学院中医药信息研究所,北京100700

出　　处：《中国实验方剂学杂志》2020年第24期161-168,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：首都卫生发展科研专项项目(2018-2-4175);国家“重大新药创制”科技重大专项(2017ZX09301018);中国中医科学院基本科研业务费自主选题项目(ZZ11-027)。

摘　　要：目的:运用网络药理学的方法,探索芪术颗粒治疗糖尿病肾病的作用机制。方法:采用中药系统药理学数据库和分析平台(TCMSP),中医百科全书数据库(ETCM),以口服生物利用度和类药性为限定条件筛选出芪术颗粒中各药的化学成分及其蛋白靶点,并通过UniProt数据库将蛋白靶点规范为相应的基因名称;通过在线《人类孟德尔遗传》数据库(OMIM),疾病-基因数据库(DisGeNET),治疗靶标数据库(TTD),ETCM数据库检索糖尿病肾病的相关基因;两者取交集之后,通过蛋白质相互作用数据库(STRING)构建蛋白互作网络,使用Cytoscape分析网络的核心靶点,使用KOBAS 3.0数据库对相关靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:从芪术颗粒中共得到化学成分93个,涉及到254个靶点,与糖尿病肾病相关的基因607个,取交集后确定了76个芪术颗粒治疗糖尿病肾病的靶标,包括蛋白激酶B1(Akt1),血管内皮生长因子α(VEGFA),白细胞介素(IL)-6,肿瘤坏死因子(TNF),丝裂原活化蛋白激酶1(MAPK1),基质金属蛋白酶(MMP)-9等核心靶点,经过GO分析和KEGG分析,芪术颗粒可以影响细胞对氮化合物的反应、调节活性氧代谢过程等生物过程,调控糖尿病并发症中的晚期糖基化终产物(AGE)/晚期糖基化终产物受体(RAGE)信号通路,流体剪切应力和动脉粥样硬化,IL-17信号通路,缺氧诱导因子-1(HIF-1)信号通路,TNF信号通路等通路。结论:芪术颗粒对糖尿病肾病的治疗作用可能是影响Akt1,VEGFA,IL-6,TNF,MAPK1,MMP-9等靶点,调控糖尿病并发症中的AGE/RAGE信号通路、流体剪切应力和动脉粥样硬化,IL-17信号通路,HIF-1信号通路,TNF信号通路等通路发挥的,可以为进一步的基础实验研究提供理论参考。Objective:To explore the mechanism of Qizhu granules in the treatment of diabetic nephropathy by using network pharmacology.Method:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database(TCMSP)and The Encyclopedia of Traditional Chinese Medicine(ETCM)database were used to screen out the chemical constituents and protein targets of each drug in the Qizhu granules based on oral bioavailability and drug-like properties.The protein target was standardized into the corresponding gene name through the UniProt database.Online Mendelian Inheritance in Man(OMIM),DisGeNET,Therapeutic Target Database(TTD),ETCM database were used to search for related targets of diabetic nephropathy,after the intersection of the two,construct a protein interaction network through protein interaction database(STRING),use Cytoscape to analyze the core target of the network,and the relevant targets were analyzed by KOBAS 3.0 database for Gene Ontology(GO)pathway enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Result:A total of 93 chemical components were obtained from Qizhu granules,involving 254 targets,and 607 targets related to diabetic nephropathy.After the intersection,76 sputum granules were determined to treat diabetic nephropathy,including protein kinase B1(Akt1),vascular endothelial growth factor(VEGFA),interleukin(IL)-6,tumor necrosis factor(TNF),mitogen-activated protein kinase 1(MAPK1),matrix metalloproteinase(MMP)-9 and other core targets,after GO analysis and KEGG analysis,Qizhu granules can affect cellular response to nitrogen compound,regulation of reactive oxygen species metabolic process and other biological processes,regulate advanced glycation end product(AGE)/advanced glycation end product receptor(RAGE)signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,IL-17 signaling pathways,HIF-1 signaling pathways TNF signaling pathways and other pathways.Conclusion:The therapeutic effect of Qizhu granules on diabetic

关 键 词：网络药理学 芪术颗粒 糖尿病肾病 信号通路 

分 类 号：R2-0[医药卫生—中医学] R289