基于数据挖掘和网络药理学的早期DN用药规律及机制分析  

Analysis of early DN medication rules and potential effects based on data mining and network pharmacology

作　　者：曲超 张冰冰[1] 姜楠[1] 张柯欣[1] 石岩[1] 张文顺[1] QU Chao;ZHANG Bingbing;JIANG Nan;ZHANG Kexin;SHI Yan;ZHANG Wenshun(Liaoning University of Traditional Chinese Medicine.Shenyang,Shenyang,110847,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《沈阳药科大学学报》2021年第5期498-512,共15页Journal of Shenyang Pharmaceutical University

基　　金：博士启动基金项目(201501093);辽宁省自然科学基金计划重点项目(20170540594)。

摘　　要：目的基于古今医案云平台挖掘现代医案治疗早期DN的用药规律并分析作用机制。方法检索中医药治疗早期DN有效验案进行数据挖掘,导入Gephi进行复杂网络分析、可视化展示,分析早期DN的常见证候及核心配伍。通过TCMSP数据库检索核心配伍的主要化合物成分和作用靶点,TTD、DisGeNET、GeneCards等数据库查询DN相关靶点。利用Cytoscape构建化合物-靶点网络、PPI网络筛选出核心靶点,进行GO注释、KEGG通路富集分析,运用PyMOL、AutoDock等进行分子对接。结果纳入112篇文献,包含150首方剂,271味中药,常见证候为气阴两虚证,核心配伍为"黄芪-山药"。筛选后得到核心化合物成分11个、靶点28个,BP条目385个,CC条目58个,MF条目139个,生物通路88条。"黄芪-山药"治疗DN存在多靶点协同作用情况,作用机制可能是通过调节PTGS2、NCOA2、PTGS1、HSP90AA1、PRSS1等核心靶点,及通过干预IL-17、TNF、Regulation of lipolysis in adipocytes、C-type lectin receptor、Endocrine resistance等相关信号通路。分子对接结果显示核心化合物成分主要与核心靶点甘氨酸,天冬酰胺,组氨酸等氨基酸残基发生氢键、疏水、范德华力等发生相互作用,结合能均低于-5.6 kcal/mol。结论气阴两虚证为DN常见证型,"黄芪-山药"为其核心配伍,中医药治疗早期DN以健脾益气、滋补肝肾之药补虚,兼顾活血化瘀、清热利湿治标,为标本同治。本研究揭示了"黄芪-山药"治疗DN的潜在分子机制,为后续研究提供理论依据及参考。Objective Based on the ancient and modern medical case cloud platform, we explored the medical rules of modern medical case treatment for early DN and analyzed the mechanism of action.Methods Retrieving effective DN cases for early treatment of traditional Chinese medicine for data mining, importing Gephi for complex network analysis and visual display, analyzing common syndromes and core compatibility of early DN.The main compound components and action targets of the core compatibility are searched through the TCMSP database, and the DN-related targets are queried by databases such as TTD,DisGeNET,and GeneCards.Cytoscape was used to construct compound-target networks and PPI networks to screen out core targets, perform GO annotation, KEGG pathway enrichment analysis, and use PyMOL,AutoDock, etc.for molecular docking.Results A total of 112 articles were included, including 150 prescriptions, including 271 traditional Chinese medicines.The common syndrome is Qi and Yin deficiency syndrome, and its core compatibility is "Astragalus-Yam".28 compounds were selected and 136 targets were obtained by intersection.After screening, 11 core compound components, 28 targets, 385 BP entries, 58 CC entries, 139 MF entries, and 88 biological pathways were obtained."Astragalus-Yam" has a multi-target synergistic effect on the treatment of DN.The mechanism of action may be through the adjustment of PTGS2,NCOA2,PTGS1,HSP90 AA1,PRSS1 and other core targets, and through the intervention of PI3 K-Akt, Endocrine resistance, MAPK,HIF-1,EGFR and other related signaling pathways.The results of molecular docking showed that the core compound components mainly interacted with the core target glycine, asparagine, histidine and other amino acid residues through hydrogen bonding, hydrophobicity, van der Waals force, etc.The binding energy was lower than-5.6 kcal/mol.Conclusion Qi-yin deficiency syndrome is a common syndrome of DN,and "Astragalus-Yam" is its core compatibility.In the early stage of traditional Chinese medicine, DN is supplemen

关 键 词：早期糖尿病肾病 数据挖掘 配伍规律 网络药理学 分子对接 

分 类 号：R28[医药卫生—中药学]