阿魏酸调控心肌肥厚的作用机制

Research on the Mechanism of Ferulic Acid in Regulating Cardiac Hypertrophy

目的:运用网络药理学与分子对接技术研究阿魏酸调控心肌肥厚的作用机制。方法:通过Gene Card、TCM、Open Targets、Swiss Target Prediction、STRING和David等数据库,筛选并构建阿魏酸调控心肌肥厚的相关靶点及蛋白互作网络PPI。将得到的共同靶点上传到David平台,进行GO(基因本体)功能富集和KEGG(京都基因百科全书)通路富集。运用Swiss Dock软件对主要靶点进行分子模拟对接,得到的结果用UCSF Chimera1.15进行分析。结果:阿魏酸作用于心肌肥厚的核心基因是STAT3、CASP3、MTOR、AR、MAPK1和ERBB2,与MAPK1、ERBB2和CASP3的亲和力最高;参与的调控生物过程包括细胞增殖调控、信号传导、调控RNA聚合酶Ⅲ启动子转录、调控Stat3蛋白酪氨酸磷酸化和磷脂酰肌醇介导的信号传导等,涉及信号通路包括缺氧诱导因子-1信号通路、Rap1信号通路、鞘脂信号通路和叉头状转录因子信号通路等。结论:阿魏酸可通过多个靶点、通路调控心肌肥厚,实际运用效果尚不清楚,仍需要深入研究。

Objective:Network pharmacology and molecular docking techniques were used to study the mechanism of ferulic acid in regulating cardiac hypertrophy.Methods:Using databases such as Gene Cards,TCM,Open targets,Swiss Target Prediction,STRING and David,we screened and constructed the relevant targets and protein interaction network PPI for ferulic acid to regulate cardiac hypertrophy.Upload the obtained common targets to the David platform for GO(Gene Ontology)functional enrichment and KEGG(Kyoto Encyclopedia of Gene Encyclopedia)pathway enrichment.Swiss Dock software was used to carry out molecular simulation docking to the main targets,and the results obtained were analyzed with UCSF Chimera 1.15.Results:The core genes that ferulic acid acts on cardiac hypertrophy are STAT3,CASP3,MTOR,AR,MAPK1 and ERBB2,and have the highest affinity with MAPK1,ERBB2 and CASP3;which participates in regulating biological processes including cell proliferation regulation,signal transduction,and regulation of RNA polymeraseⅢ.Promoter transcription,regulation of Stat3 protein tyrosine phosphorylation and phosphatidylinositol-media ted signal transduction,etc.,involving signaling pathways including hypoxia-inducible facto r-1 signaling pathway,Rapl signaling pathway,sphingolipid signaling pathway,and forkhead transcription Factor signaling pathway,etc.Conclusion:Conclusion:Ferulic acid cloud regulate myocardial hypertrophy through multiple targets and pathways.The actual application effect was still unclear,and further study was still needed.