赤芍治疗糖尿病视网膜病变的网络药理学研究

Network Pharmacologic Study of Radix Pae-oniae Rubra in the Treatment of Diabetes Retinopathy

摘要: 目的：应用网络药理学研究赤芍治疗糖尿病视网膜病变(diabetes retinopathy, DR)的潜在作用机制。方法：通过中药系统药理学数据库及分析平台(TCMSP)筛选出赤芍的活性成分及潜在靶点，通过GeneCards、OMIM、TTD、PharmGKB、DrugBank数据库挖掘糖尿病视网膜病变的相关靶点。应用Cytoscape 3.9.1软件构建赤芍成分–靶点相互作用网络图。应用韦恩图获取药物和疾病的交集靶点。将交集靶点上传至metascape，对交集靶点进行GO和KEGG富集分析。对交集靶点进行网络拓扑分析，并应用Cytoscape 3.9.1软件的centiscape插件筛选出关键靶点。结果：共查找到符合筛选条件的药物成分29种，获得潜在靶点99个，共获得疾病相关靶点859个，药物–疾病交集靶点32个；利用网络拓扑分析最终筛选出CASP3、ESR1、AR、TP53、VEGFA、CAT、TNF、AKT1、IL6共9个关键靶点。分析得出赤芍治疗糖尿病视网膜病变的关键靶点主要被富集在AGE-RAGE、HIF-1、PI3K-Akt、Fluid shear stress and atherosclerosis、NF-κB等信号通路。结论：本研究结果初步验证和预测了赤芍对治疗DR的作用机制，为进一步临床验证及药理实验提供参考。

Abstract: Objective: To investigate the potential mechanism of network pharmacology in the treatment of diabetes retinopathy (DR). Methods: The active constituents and potential targets of Radix Paeoniae Rubra were screened out by the Chinese Traditional Medicine System Pharmacology (TCMSP) data-base. The related targets of DR were mined through GeneCards, OMIM, TTD, PharmGKB, and Drug-Bank databases. The drug composition-target interaction network diagram was constructed by us-ing Cytoscape 3.9.1 software. The intersection targets of drugs and diseases were obtained by the Venn diagrams. The intersection targets were uploaded to metascape for GO and KEGG enrichment analysis. Network topology analysis was carried out on intersection targets and the key targets were screened by using centiscape plug-in of Cytoscape 3.9.1. Results: A total of 29 drug ingredients meeting the screening conditions were identified; 99 potential targets and a total of 859 dis-ease-related targets were obtained. There were 32 drug-disease intersection targets. Nine key tar-gets including CASP3, ESR1, AR, TP53, VEGFA, CAT, TNF, AKT1, and IL6 were selected by network topology analysis. The analysis results indicated that the key targets of Radix Paeoniae Rubra in DR were mainly concentrated in AGE-RAGE, HIF-1, PI3K-Akt, Fluid shear stress and atherosclerosis, and NF-κB signaling pathways. Conclusions: The results of this study preliminarily verify and predict the mechanism of action of Radix Paeoniae Rubra in the treatment of DR, and provide a reference for further clinical validation and pharmacological experiments.