基于网络药理学和细胞实验探讨大黄酚激活PI3K/AKT信号通路改善心肌梗死的作用机制

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AbstarctObjective：Toexploretheimprovingeffctsofchysophanol（CHR）onmyocardialinfarction（Ml）damageanditsmolecular mechanisms.Metods：Thepotentialtargetsofchrysophanolwereobtainedusing thePubChemandSwissTargetPredictiondatabases. Ml-relatedtargetgeneswrecolectedrotheGeneCardsdatabase.Teintersectionoftosetsasusedtoidentifypotentiagetsfor ChrysophanolintheimprovementofMI.hesetargetsweresubjectedtogenefunctionannotation（geneontology，GO）andKyoto Encyclopediaof Genesand Genomes（KEGG）enrichment analysis.The STRINGdatabaseandCytoscape3.9.1software wereusedto consructprotei-proteininteractioP）etworkiagramsandidentifypotetialoretagetsfoCysopanolintreatingolecular dockingandbindingafitypredictionbetweenChrysophanolandthecoretargetswereperformedusingtheSchdingersofareand visualizationwasdoneusingPyMOL.Finaly，primaryneonatalratcardiomyocytesNRCMs）weresubjectedtooxygenandglucose deprivation（OGD）for toestablishacellmodelofMl.Proteinexpressionrelated targetswasdetected bywesternblot，andterminal deoxynucleotidyltransferase-mediatednickendlabelingTUNEL）anddiydroethidium（DHE）stainingwereusedtodetectapoptosisnd oxidativestressinardioycytesesuls：Atotalof47intersectiotargetsetweenchsopaolandMwereidentiKndGO enrichmentanalysisshowedthatchrysophanolmightprotectMlagainstdamagebyinhibitingapoptosisandoxidativestressin cardiomyocytes，whichwasoselyrlatedtophospatidyinosiol-3-kinase（Pl3K）proteinkinaseB（AKT）pathway.Furtherrsarch identiedSRCatixtalpotenase9（9）-2strogreceptor（1）atsockprote990）A1，9AB andmammaiantargetofrapamcinproteinOR）aspotentialcoretargetsforchsoanolintreatingMMoleculardockingsowdeter bindingafityetweenchsopanolandthoretargetsswellaste3/AKpathwayelatedmleculepospati-dyoi4 5-bisphosphate3-kinasecatayticsubunitalpaK3C）ExperimentavalidatiodemonstratedthatchsoanolactivatedthePl3K/A pathwaybyGDinardiomyoctes.AditionalyDandUNELstainingresutsinicatedatcsoanolcouldlviateidive stress and apoptosis induced by OGD in cardiomyocytes （ P<0.01 ）.However，pretreatment with LY294002（a Pl3K inhibitor） significantly weakened theeffectsof chrysophanol ininhibitingoxidative stress and apoptosis（ P<0.01. .Conclusion：Chrysophanol protects cardiomyocytesagaistoxidativetressandapoptosisbyactivatingPl3K/AKsignalingpataytherebyimprovingmyocardialarctio

Keywords myocardialinfarction；chrysophanol;cardiomyocytesapoptosis；oxidativestress；networkpharmacology；experimental verification

心肌梗死是心血管疾病的重要危险因素之一，随着人口老龄化进程的加快和不健康生活方式的影响，心肌梗死患病人数呈现快速增长的趋势，并向低龄化方向发展[1]。（剩余15057字）