基于网络药理学和数据挖掘探讨中药调控铁死亡干预肝硬化的用药规律研究

Regulation of Ferroptosis by Traditional Chinese Medicine in the Intervention of Liver Cirrhosis Based on Network Pharmacology and Data Mining

目的:运用网络药理学和数据挖掘技术,探索中药调控铁死亡干预肝硬化的用药规律,为肝硬化铁死亡的相关研究提供参考。方法:利用GeneCards、GeneCLiP3和FerrDb数据库获取铁死亡的强相关靶点,通过GeneCards和DisGeNET数据库获取肝硬化疾病靶点,两者映射得到肝硬化铁死亡的相关靶点;对潜在靶点进行蛋白质-蛋白质相互作用(PPI)分析,选取Degree值≥2倍中位数的靶点(潜在靶点)通过中药系统药理学数据库与分析平台获取相关化合物和中药,利用R语言对潜在靶点进行相关机制分析;利用Cytoscape 3.7.2软件构建潜在靶点PPI网络图、靶点-化合物网络图、靶点-化合物-中药网络图;利用分子对接验证靶点与化合物以及中药核心成分的结合活性;借助中医传承辅助平台分析候选中药的性味归经及功效。结果:共得到肝硬化铁死亡相关靶点225个,Degree值≥36的肝硬化铁死亡的潜在靶点有47个,筛选得到146个化合物和284味中药,靶点与化合物及中药的核心成分结合较稳定,候选中药以寒性、苦味、入肝经、清热类、补虚类及活血化瘀类为主。结论:本研究从肝硬化和铁死亡的靶点出发,挖掘调控铁死亡干预肝硬化的中药及用药规律,也探讨了肝硬化铁死亡的相关作用机制,可为肝硬化铁死亡的相关研究提供参考。

OBJECTIVE:To explore the medication rules of traditional Chinese medicine(TCM)in the intervention of liver cirrhosis by regulating ferroptosis based on network pharmacology and data mining,so as to provide reference for related researches on ferroptosis in liver cirrhosis.METHODS:GeneCards,GeneCLiP3 and FerrDb database were used to obtain the strongly correlated targets of ferroptosis,GeneCards and DisGeNET database were applied to obtain the correlated targets of ferroptosis in liver cirrhosis,the correlated targets of ferroptosis in liver cirrhosis were received by mapping the above two targets.Protein-protein interaction(PPI)analysis was performed for potential targets.And targets with Degree value≥2 times median(potential targets)were selected to obtain related compounds and TCM through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Correlation mechanism analysis were performed on potential targets by using R language.Cytoscape 3.7.2 software was used to construct PPI network diagram of potential targets,targets-compounds network diagram and targets-compounds-TCM network diagram.Molecular docking was used to verify the binding activity of the targets to the compound and core prescription of TCM.The Chinese Medicine inheritance auxiliary platform was used to analyze the sexual taste,meridian and efficacy of candidate TCM.RESULTS:A total of 225 targets related to ferroptosis in liver cirrhosis were obtained,and 47 potential targets of ferroptosis in cirrhosis with Degree value≥36 were obtained.Totally 146 compounds and 284 TCM were screened,the binding activity of the targets to compound and the core prescription of TCM were stable,candidate TCM were mainly cold,bitter taste,liver meridian,heat-cleaning medicinal,tonify deficiency and blood-activating and stasis-resolving medicinal type.CONCLUSIONS:From the targets of liver cirrhosis and ferroptosis,this study explores the regulation of ferroptosis by TCM in the intervention of liver cirrhosis and medication rules,and also analyzes the relevant mechanism of ferroptosis in liver cirrhosis,which provides reference for related research on ferroptosis in liver cirrhosis.