基于网络药理学与分子对接探讨中药复方益肾康治疗糖尿病肾病机制  

Discussion on the Mechanism of Traditional Chinese Medicine Compound Yishenkang(益肾康)in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

作　　者：张颖[1,2] 黄奡[2] 宫成军 张兰[2] ZHANG Ying;HUANG Ao;GONG Chengjun;ZHANG Lan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;AffiliatedHospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《辽宁中医药大学学报》2022年第9期131-136,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：全国名老中医药专家传承工作室建设项目(2022-75);辽宁省自然科学基金(2019-ZD-0439);辽宁中医药大学附属医院“育苗工程”项目(YM202119);辽宁省中医药临床学(专)科能力建设项目(2018-125)。

摘　　要：目的通过分析中药复方益肾康颗粒的有效化学成分,研究其治疗糖尿病肾病(diabetic nephropathy,DN)的作用机制。方法应用中药系统药理学数据库分析平台(TCMSP)数据库对中药复方益肾康中的化学活性物质和靶点信息进行检索、挖掘与筛选,同时应用基因组注释数据库平台(Genecards)预测DN的作用靶点,并运用uniprot数据库查询明确各靶点的基因名称,构建活性成分-靶点网络图。然后分别应用String数据库平台构建蛋白互作关系(protein-protein interaction,PPI)图,最后利用Bioconductor平台和R语言进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析,并构建靶点-通路网络图,基于上述研究得出的结果进行分子对接分析。结果中药复方益肾康颗粒作用于DN的关键化学成分27个,共同靶点72个,通过PPI蛋白互作关系得到AKT1、MAPK1、MAPK14等15个核心基因;GO富集分析结果包括脂多糖应答、膜筏、细胞因子受体结合等;KEGG富集通路包括糖尿病并发症中的AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、TNF信号通路、IL-17信号通路、MAPK信号通路等。分子对接结果显示受体MAPK1与槲皮素、木犀草素、山柰酚对接能分别为-4.40、-5.54、-4.76 kJ/mol;受体AKT1与槲皮素、木犀草素、山柰酚的对接能分别为-7.43、-7.35、-7.17 kJ/mol,化合物与靶点能稳定地结合并发生相互作用。结论中药复方益肾康颗粒可通过调节MAPK1、AKT1、MAPK14等靶点,调控AGE-RAGE、TNF、IL-17、MAPK等信号通路而影响血管内皮通透性,调控细胞分裂,抑制炎症反应,进而对DN起到治疗作用。Objective To analyze the effective chemical constituents of Yishenkang Granules(益肾康颗粒),a traditional Chinese medicine,to study its mechanism of action in the treatment of diabetic nephropathy(DN).Methods Using the TCM System Pharmacology Technology Platform(TCMSP)database to search,mine and screen the chemical active substances and target information in the Chinese medicine compound Yishenkang.At the same time,use the genome annotation database platform(GeneCards)to predict the target of DN,And use the uniprot database to query and clarify the gene name of each target,and construct an active ingredient-target network diagram.Then use the String database platform to construct the PPI protein interaction relationship diagram,and finally use the Bioconductor platform and R language to carry out GO enrichment analysis and KEGG enrichment analysis,and construct the target-pathway network diagram,and carry out based on the results obtained from the above research Molecular docking analysis.Results Traditional Chinese medicine compound Yishenkang Granules acted on 27 key chemical components of DN,with 72 common targets.15 core genes such as AKT1,MAPK1,MAPK14 were obtained through protein-protein interaction(PPI);Gene ontology(GO)enrichment analysis results included lipopolysaccharide response,membrane rafts,cytokine receptor binding,etc;Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway includes AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,TNF signaling pathway,IL-17 signaling pathway,MAPK signaling in diabetic complications access,etc.The molecular docking results showed that the docking energies of receptor MAPK1 with quercetin,luteolin,and kaempferol were-4.40,-5.54,-4.76 kJ/mol,respectively;receptor AKT1 and xyloquercetin,luteolin docking energies of grass element and kaempferol were-7.43,-7.35,and-7.17 kJ/mol,respectively,and the compound can bind and interact with the target stably.Conclusion Traditional Chinese medicine compound Yishenkang granules can affect the permea

关 键 词：网络药理学 益肾康 糖尿病肾病 数据挖掘 化学成分 基因靶点 分子对接 作用机制 

分 类 号：R587.2[医药卫生—内分泌]