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作 者:崔家霖 高彦彬[1,2] CUI Jialin;GAO Yanbin(College of TCM,Capital Medical University,Beijing 10069;Beijing Key Laboratory of TCM Collateral Disease Theory Research,Beijing 10069)
机构地区:[1]首都医科大学中医药学院,北京100069 [2]中医络病研究北京市重点实验室,北京100069
出 处:《中药新药与临床药理》2021年第7期979-987,共9页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:国家重点基础研究发展计划(973计划)项目(2012CB518602);国家重点基础研究发展计划(973计划)项目(2018YFC1704102)——《基于“道术结合”思路与多元融合方法的名老中医经验传承创新研究》子课题《东部地区名老中医学术观点、特色诊疗方法和重大疾病防治经验研究》。
摘 要:目的基于网络药理学方法分析临床治疗糖尿病肾病(DN)的有效方剂水陆二仙丹治疗糖尿病肾病的药理机制,为其临床运用和新药研发提供参考。方法结合文献,通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取芡实、金樱子的主要化学成分及其靶点,根据ADME筛选中药活性组分;通过GenCards、OMIM、TTD、DRUGBANK数据库获取糖尿病肾病主要靶点,利用STRING平台进行蛋白质相互作用分析,而后采用Cytoscape 3.8.0软件构建"中药-成分-疾病-靶点"网络。构建PPI网络并挖掘网络中潜在的蛋白质功能模块。采用R 3.6.0分析"药物-成分-靶点-疾病"及其参与的生物过程及通路。结果水陆二仙丹治疗糖尿病肾病的核心活性成分为β-谷甾醇、槲皮素、山柰酚、维生素E等,核心靶点有AKT1、MAPK1、PTGS2、JUN等,水陆二仙丹治疗糖尿病肾病生物学通路主要作用于AGE-RAGE信号通路、TNF通路、VEGF通路等,其功能主要为调节细胞内激素受体的生命活动等。结论本研究初步揭示了水陆二仙丹治疗糖尿病肾病的多成分、多靶点、多通路的作用机制,为水陆二仙丹后续研究和临床应用提供了理论基础。Objective To analyze the effective prescription for clinical treatment of diabetic nephropathy(DN)based on network pharmocology and explore the pharmacological mechanism of Shuilu Erxian Dan in the treatment of DN.The aim of this study is to provide reference for clinical application and new drug development.Methods TCMSP(traditional Chinese medicine systems pharmacology database and analysis platform)was used to obtain the main chemical components and targets of Euryale ferox and Rosa laevigata,and the active components of traditional Chinese medicine were screened according to ADME.The main targets of DN were obtained from GenCards,OMIM,TTD and DRUGBANK databases,and the protein-protein interaction was analyzed by STRING platform,and then the network of"drug-composition-target-disease"was constructed by using the software of Cytoscape 3.8.0.PPI network was constructed and potential protein functional modules were mined.R 3.6.0 was used to analyze the biological process and pathway of"traditional Chinese medicine-component-disease-target".Results The core active components in the treatment of DN wereβ-sitosterol,quercetin,kaempferol,vitamin E,etc.,the core targets were AKT1,MAPK1,PTGS2,JUN,etc.The biological pathway of Shuilu Erxian Dan in treating DN mainly involved in AGE-RAGE signal pathway,TNF pathway and VEGF pathway,and its function was to regulate the life activity of hormone receptor in cells.Conclusion This study preliminarily revealed the mechanism of multi-component,multi-target and multi-channel of Shuilu Erxian Dan in the treatment of DN,which provided a theoretical basis for the follow-up research and clinical application of the drug.
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