基于网络药理学的复方丹参滴丸治疗糖尿病视网膜病变的作用机制研究  

Mechanism on treatment of diabetic retinopathy with Compound Danshen Dripping Pills based on network pharmacology

作　　者：王妙然 李秋艳[1] 马学竹 王旭杰 张雪雪 张蕊[1,2] WANG Miaoran;LI Qiuyan;MA Xuezhu(Xi Yuan Hospital,China Academy of Chinese Medical Sciences,Beijing 10091,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]北京中医药大学,北京100029 [3]北京市中西医结合医院,北京100039 [4]中国中医科学院,北京100700

出　　处：《中国中医眼科杂志》2020年第4期293-302,共10页China Journal of Chinese Ophthalmology

基　　金：“核高基”国家科技重大专项(01专项)资助(2018ZX01031201)。

摘　　要：目的通过网络药理学方法预测复方丹参滴丸治疗糖尿病视网膜病变的多成分、多靶点、多途径的作用机制。方法基于中药系统药理(TCMSP)数据库,以口服利用度(OB),类药性(DL)筛选复方丹参滴丸中的活性成分。依据反向药效团匹配(PharmMapper)方法预测复方丹参滴丸活性成分靶点;通过GeneCards数据库中与糖尿病视网膜病变相关靶基因对比筛选,通过STRING数据库结合Cytoscape软件绘制蛋白相互作用(PPI)网络并进行网络拓扑学分析,然后借助生物信息学数据库(Metascape)及DAVID数据库对靶点进行GO生物学过程、分子功能、细胞组分分析和KEGG通路分析,Cytoscape3.7.2软件构建并分析复方丹参滴丸“活性成分-靶点-通路”网络。结果发现复方丹参滴丸共有50个活性成分和429个靶点,DR共有821个已知的治疗靶点,将药物靶点与疾病靶点映射后共获得98个共有靶点。PPI蛋白互作网络分析发现ALB、AKT1、MMP9、MAPK1等可能是复方丹参滴丸治疗DR的核心靶点。GO富集分析确定了60个条目,KEGG通路富集分析确定了108条相关信号通路,主要有PI3K-Akt信号通路、Ras信号通路、Rap1信号通路、MAPK信号通路、FoxO信号通路、VEGF信号通路以及HIF-1信号通路等。结论复方丹参滴丸对治疗DR具有多途径、多靶点作用的特点。其可能是通过影响细胞代谢、抗炎、免疫调节、促进血管新生、改善无氧代谢等途径发挥治疗作用,为进一步阐释复方丹参滴丸治疗DR的药理机制提供了理论依据。OBJECTIVE To predict the multi-component,multi-target and multi-pathway mechanism of Compound Danshen Dripping Pills in treating diabetic retinopathy(DR)based on the method of network pharmacology.METHODS In view of Traditional Chinese Medicine systems pharmacology(TCMSP)database,the main active components of Compound Danshen Dripping Pills were screened by oral bioavailability(OB)and Drug-likeness(DL).The targets of active components of Compound Danshen Dripping Pills were predicted based on the method of PharmMapper.Through the comparative screening of GeneCards database and related target gene of DR,by using the STRING database and Cytoscape3.7.2 software,the protein interaction(PPI)network was plotted and analyzed.Then GO biological process,molecular function,cell component analysis and KEGG pathway analysis of the target were carried out with the help of Metascape and DAVID databases,and the active compounds-target-pathway network of Compound Danshen Dripping Pills was constructed and analyzed by Cytoscape3.7.2 software.RESULTS The prediction results showed that there were 50 active components and 429 targets in Compound Danshen Dripping Pills and there were 821 known therapeutic targets in DR,and 98 common targets were obtained by mapping drug targets and disease targets.PPI protein interaction network analysis showed that ALB,AKT1,MMP9,MAPK1 and others might be the core target of Compound Danshen Dripping Pills in the treatment of DR.GO enrichment analysis identified 60 items,and KEGG pathway enrichment analysis identified 108 related signaling pathways,which mainly included PI3K-Akt signaling pathway,Ras signaling pathway,Rap1 signaling pathway,MAPK signaling pathway,FoxO signaling pathway,VEGF signaling pathway and HIF-1 signaling pathway.CONCLUSIONS Compound Danshen Dripping Pills have the characteristics of multi-pathways and multi-target effects on treating DR.Compound Danshen Dripping Pills could exert anti-DR effect by influencing cell metabolism,anti-inflammatory,immune regulation,promoting angioge

关 键 词：糖尿病视网膜病变 网络药理学 复方丹参滴丸 作用机制 药效团匹配与潜在识别靶标平台 

分 类 号：R285[医药卫生—中药学]