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基于铁死亡角度治疗心力衰竭中药的筛选

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目的:通过生物信息学从铁死亡角度筛选治疗心力衰竭的中药,为心力衰竭的治疗开辟新途径。方法:在 GEO数据库中检索与心力衰竭相关的符合条件的数据集,利用 R软件进行 limma差异分析获得心力衰竭的差异表达靶点,在 FerrDb平台收集与铁死亡相关靶点,将铁死亡靶点与心力衰竭差异表达靶点取交集后构建蛋白互作(PPI)网络,并对该网络进行拓扑学性质分析,利用 R软件对共同靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析。借助 HERB数据库检索共同靶点对应的天然药物成分和中药,利用 AutoDock软件对天然药物成分及其所对应靶点后进行分子对接。结果:GEO数据库筛选出数据集 2 个,通过 limma差异分析后得到 14 093个靶点,得到与铁死亡相关靶点 214 个,铁死亡与心力衰竭差异表达靶点取交集得到共同靶点176个,利用共同靶点构建 PPI网络与拓扑学性质分析得到关键靶点抑癌基因(TP53)、原癌基因(JUN)、泛素 C(UBC)、腺苷酸活化蛋白激酶(MAPK)14、MAPK3、信号转导与转录激活蛋白 3(STAT3)、表皮生长因子受体(EGFR)等。GO及 KEGG富集分析显示心力衰竭的发病从铁死亡角度或与细胞对化学应激的反应、对氧化应激的反应、次级溶酶体、黑色素体、自噬体、线粒体外膜、基底质膜核、氧化还原酶活性、铁离子结合、脂质和动脉粥样硬化、叉头转录因子(FoXO)信号通路等相关。检索HERB数据库结果显示,黄连素、醉茄素 A、血根碱等近 80种天然药物成分以及白鲜皮、半枝莲、苍术、穿心莲、防风等 100 余种中药或可通过作用于关键靶点治疗心力衰竭。分子对接结果显示 JUN与黄连素、MAPK14与醉茄素 A、MAPK3与血根碱结合较好。结论:通过生物信息学研究发现,黄连素、醉茄素 A、血根碱等天然药物成分以及黄连、防己、黄柏、延胡索、牛膝、吴茱萸、黄芪、丹参等中药或可作用于 TP53、MAPK14、MAPK3、JUN、STAT3等靶点治疗心力衰竭。
Chinese Herbs for Treatment of Heart Failure Based on the Perspective of Iron Death
Objective:To screen traditional Chinese medicine for the treatment of heart failure(HF)based on the perspective of iron death.Methods:HF related eligible datasets in GEO database were retrieved,limma differential analysis were carry out to obtain HF differential expression targets using R software,iron death related targets were collected on FerrDb platform,protein-protein interaction network was constructed after intersection(PPI)of iron death targets and HF differential expression targets,and topological properties of the network were analyzed.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for common targets using R software.The HERB database was used to search the compounds and traditional Chinese medicine corresponding to the common target,and the small molecule compounds and their corresponding targets were used to carry out molecular pairs.Results:Two datasets were screened from GEO database,there were 14 093 targets obtained through limma differential analysis,214 targets related to iron death were obtained through collection,176 targets were obtained through intersection of iron death and HF differential expression targets,and key targets TP53,JUN,UBC,MAPK14,MAPK3,STAT3,EGFR,etc.were obtained through PPI network construction and topological property analysis of common targets of iron death and HF differential expression.The enrichment analysis of GO and KEGG showed that HF was related to cell response to chemical stress,oxidative stress,secondary lysosome,melanosome,autophage,outer membrane of mitochondria,nucleus of basement membrane,oxidoreductase activity,iron binding,lipid and atherosclerotic,FoXO signal pathway,etc.from the perspective of iron death.The results of searching HERB database showed that nearly 80 kinds of compounds of natural drugs,such as berberine,withaferin A,sanguinarine,and more than 100 kinds of traditional Chinese medicines,such as cortex dictamni,scutellaria barbata,atractylodes,andrographis paniculata,and fangfeng could be used to treat HF by acting on key targets.Molecular docking results showed that JUN and berberine,MAPK14 and withaferin A,MAPK3 and sanguinarine could well combine.Conclusion:Through bioinformatics research,it is found that with berberine,withaferin A,sanguinarine and other compounds,as well as some traditional Chinese medicines such as Coptis,Radix Stephaniae,Cortex Phellodendri,Rhizoma Corydalis,Radix Achyranthes,Fructus Evodiae,Radix Astragali,Radix Salviae Miltiorrhizae can act on TP53,MAPK14,MAPK3,JUN,STAT3,and other targets to treat HF.

heart failureiron deathbioinformaticstargetsChinese herbs

施敏、魏佳明、袁惠、郭志华

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湖南中医药大学慢病中医智能诊断与治未病湖南省重点实验室(长沙 410208)

心力衰竭 铁死亡 生物信息学 靶点 中药

国家自然科学基金湖南省重点研发计划"一方"研究生创新项目湖南省研究生创新项目

821743432022SK20122023YF10QL20230197

2024

中西医结合心脑血管病杂志
中国中西医结合学会 山西医科大学第一医院

中西医结合心脑血管病杂志

CSTPCD
影响因子:1.463
ISSN:1672-1349
年,卷(期):2024.22(2)
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