摘要
目的:预测表没食子儿茶素没食子酸酯(Epigallocatechin gallate, EGCG)治疗肺动脉高压(Pulmonary Hypertension, PH)的机制。方法:从SwissTargetPrediction和GeneGards数据库得到EGCG相关靶点与GeneGards中获得的PH相关靶点取交集。将该交集数据导入Metascape数据库进行GO功能注释和KEGG通路富集分析并利用STRING数据库获取交集靶点间蛋白互作(protein-protein interaction,PPI)网络,导入Cytoscape 3.10.3软件进行分析,以筛选出核心靶点,最后通过AutoDock Vina软件对核心靶点进行分子对接。结果:筛选出104个EGCG与PH的交集靶点,Cytoscape 3.10.3软件分析后得到4个核心靶点:TP53、AKT1、STAT3、JUN。分子对接发现核心靶点与EGCG的结合能力均较强,其中TP53的结合能力最强。GO生物学过程分别为细胞运动的正调节、对氧气的反应、调节平滑肌细胞增殖等。KEGG富集通路包括:癌症通路、脂质与动脉粥样硬化、MAPK信号通路等,其中MAPK富集的靶点数最多。结论:EGCG可能通过TP53、AKT1、STAT3、JUN等靶点,MAPK通路调节平滑肌细胞增殖治疗pH。
Objective:To predict the mechanisms of Epigallocatechin gallate(EGCG)in the treatment of pulmonary hypertension(PH).Methods:To identify the genes associated with EGCG,the SwissTargetPrediction and GeneGards databases were utilized.Meanwhile,PH-related target genes were also gained from the GeneGards.Subsequently,the Metascape platform was applied to conduct GO functional annotation and KEGG pathway enrichment analysis on the overlapping targets.The STRING was implemented to construct a protein-protein interaction(PPI)network of the intersection targets.Cytoscape 3.10.3 was used for visualization and topology analysis to identify potential key targets.The key targets identified were subsequently validated through molecular docking using AutoDock.Results:A total of 104 targets associated with both EGCG and PH were identified.Following further analysis,four key targets were determined:TP53,AKT1,STAT3,JUN.Molecular docking verification revealed that EGCG exhibits a strong binding affinity for these four key target genes and TP53 had the smallest binding energy.The GO biological process results highlighted positive regulation of cell movement,response to oxygen,and regulation of smooth muscle cell proliferation et al.KEGG analysis revealed enriched pathways,including cancer pathways,lipids and atherosclerosis,and MAPK signaling pathways which was the most enriched target.Conclusion:EGCG may have therapeutic potential for PH by regulating TP53,Akt1,STAT3,JUN and MAPK pathway.
作者
何芳
傅敏
刘小辉
He Fang;Fu Min;Liu Xiaohui(Affiliated Nanhua Hospital,Hengyang Medical School,University of South China,Hengyang 421002,China)
出处
《广东化工》
2026年第1期55-59,共5页
Guangdong Chemical Industry
基金
2024年湖南省自然科学基金青年科学基金项目(2024JJ6410)
2024年湖南省卫生健康委卫生科研课题资助项目(W20243230)
2024年衡阳市指导性计划(社会发展领域)(202424017549)。
