基于网络药理学与实验验证探讨肉桂酸治疗慢性心力衰竭的作用机制  

Mechanism of Action of Cinnamic Acid in Treatment of Chronic Heart Failure:A Study Based on Network Pharmacology and Experimental Validation

作　　者：魏科东 吴婉婉 丁芮 任涵 赵婉竹 陈明[1] 周鹏[1,3] 王靓 黄金玲[1,3] WEI Kedong;WU Wanwan;DING Rui;REN Han;ZHAO Wanzhu;CHEN Ming;ZHOU Peng;WANG Liang;HUANG Jinling(School of Integrated Traditional Chinese and Western Medicine,Anhui University of Chinese Medicine,Anhui Hefei 230012,China;College of Traditional Chinese Medicine,Anhui Hefei 230012,China;Key Laboratory of Chinese Medicinal Formula of Anhui Province,Anhui University of Chinese Medicine,Anhui Hefei 230012,China)

机构地区：[1]安徽中医药大学中西医结合学院,安徽合肥230012 [2]安徽中医药大学中医学院,安徽合肥230012 [3]中药复方安徽省重点实验室,安徽合肥230012

出　　处：《安徽中医药大学学报》2024年第3期65-73,共9页Journal of Anhui University of Chinese Medicine

基　　金：国家自然科学基金项目(81973844,81373533)。

摘　　要：目的采用网络药理学、分子对接及体外实验验证的方法,探讨肉桂酸治疗慢性心力衰竭(chronic heart failure,CHF)的潜在靶点及作用机制。方法通过网络药理学在线数据库预测肉桂酸靶点及CHF靶点,取交集靶点于String数据库构建蛋白互作网络,通过Cytoscape 3.7.2软件进行可视化分析,筛选出核心靶点,使用Metascape数据库进行GO和KEGG富集分析,预测肉桂酸治疗CHF的作用机制,采用分子对接技术及体外实验验证上述结果。结果网络药理学分析结果发现,肉桂酸潜在靶点187个,与6094个CHF疾病靶点相交,得到132个交集靶点,涉及CASP3、JUN、PTGS2、MMP9、TLR4等10个核心靶点。GO和KEGG富集分析显示,肉桂酸治疗CHF的作用主要与细胞对活性氧的反应、对氧化应激的反应等生物过程有关,涉及细胞凋亡等信号通路。分子对接结果显示,肉桂酸与10个核心靶点均具有良好的结合活性。体外实验结果显示,肉桂酸能显著降低心肌细胞H9c2凋亡率及活性氧水平(P<0.05),降低c-Jun、PTGS2、MMP9、TLR4 mRNA表达水平(P<0.05)和caspase-9、caspase-3、Bax蛋白表达水平(P<0.05),升高Bcl-2蛋白表达水平(P<0.05);使用乙酰半胱氨酸后,细胞凋亡率、活性氧水平及Bax蛋白表达水平显著降低(P<0.05),Bcl-2蛋白表达水平显著升高(P<0.05),与肉桂酸作用一致。结论肉桂酸能够调节多个信号靶点、抑制心肌细胞氧化应激损伤及细胞凋亡,发挥治疗CHF的作用,肉桂酸是苓桂术甘汤防治CHF的重要物质基础之一。Objective To investigate the potential targets and mechanism of action of cinnamic acid in the treatment of chronic heart failure(CHF)based on network pharmacology,molecular docking,and in vitro experimental validation.Methods Online databases of network pharmacology were used to predict the targets of cinnamic acid and CHF,and the intersecting targets were used to construct a protein-protein interaction network in String database.Cytoscape 3.7.2 software was used to perform a visual analysis and obtain the core targets,and Metascape database was used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses and predict the mechanism of action of cinnamic acid in the treatment of CHF.Molecular docking and in vitro experiment were used to validate the above results.Results Network pharmacology analysis obtained 187 potential targets of cinnamic acid,which were intersected with 6094 disease targets of CHF,and 132 intersecting targets were obtained,involving 10 core targets such as CASP3,JUN,PTGS2,MMP9,and TLR4.GO and KEGG enrichment analyses showed that cinnamic acid was associated with the biological processes such as cellular response to reactive oxygen species(ROS)and cellular response to oxidative stress and was involved in the signaling pathways including cell apoptosis.Molecular docking showed that cinnamic acid had good binding activity to 10 core targets.The in vitro experiment showed that cinnamic acid significantly reduced the apoptosis rate of H9c2 cardiomyocytes,the level of ROS(P<0.05),the mRNA expression levels of c-Jun,PTGS2,MMP9,and TLR4(P<0.05),and the protein expression levels of caspase-9,caspase-3,and Bax(P<0.05),and it significantly increased the protein expression level of Bcl-2(P<0.05).After the application of N-acetylcysteine(NAC),there were significant reductions in cell apoptosis rate,ROS level,and the protein expression level of Bax(P<0.05)and a significant increase in the protein expression level of Bcl-2(P<0.05),suggesting that NAC had a similar ef

关 键 词：肉桂酸 慢性心力衰竭 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]