北京中科医院好不好 https://m-mip.39.net/baidianfeng/mipso_4635657.htmlModulationoftheacutedefencereactionbyeplerenonepreventscardiacdiseaseprogressioninviralmyocarditisESCHeartFailureArticleEarlyRecent,July14,./ehf2.本文由“天纳”临床学术信息人工智能系统自动翻译点击文末“阅读原文”下载本文PDFAimsLeftventricular(LV)dysfunctioninviralmyocarditisisattributedtomyocardialinflammationandfibrosis,inducingacuteandlong‐timecardiacdamage.Interventionsarenotestablished.Onthebasisofthelinkbetweeninflammation,fibrosis,aldosterone,andextracellularmatrixregulation,weaimedtoinvestigatetheeffectofanearlyinterventionwiththemineralocorticoidreceptorantagonist(MRA)eplerenoneoncardiacremodellinginamurinemodelofpersistentcoxsackievirusB3(CVB3)‐inducedmyocarditis.病毒性心肌炎的左心室功能障碍是由于心肌炎症和纤维化引起的急性和长期心脏损害。干预措施尚未建立。基于炎症、纤维化、醛固酮和细胞外基质调节之间的联系，我们旨在研究早期干预盐皮质激素受体拮抗剂（MRA）依普利酮对持续性柯萨奇病毒B3（CVB3）诱导的心肌炎小鼠心脏重构的影响。MethodsandresultsSWR/Jmicewereinfectedwith5?×?plaque‐formingunitsofCVB3(Nancystrain)anddailytreatedeitherwitheplerenone(?mg/kgbodyweight)orwithplacebostartingfromDay1.AtDay8or28postinfection,micewerehaemodynamicallycharacterizedandsubsequentlysacrificedforimmunohistologicalandmolecularbiologyanalyses.EplerenonedidnotinfluenceCVB3load.AlreadyatDay8,1.8‐fold(P??0.05),1.4‐fold(P??0.05),3.2‐fold(P??0.01),and2.1‐fold(P??0.)reductioninLVintercellularadhesionmolecule1expression,presenceofmonocytes/macrophages,oxidativestress,andapoptosis,respectively,wasobservedineplerenone‐treatedvs.untreatedCVB3‐infectedmice.Invitro,eplerenoneledto1.4‐fold(P??0.01)and1.2‐fold(P??0.01)lessCVB3‐inducedcardiomyocyteoxidativestressandapoptosis.Furthermore,collagenproductionwas1.1‐fold(P??0.05)decreasedincardiacfibroblastsculturedwithmediumofeplerenone‐treatedvs.untreatedCVB3‐infectedHL‐1cardiomyocytes.Theseameliorationswereinvivotranslatedintopreventionofcardiacfibrosis,asshownby1.4‐fold(P??0.01)and2.1‐fold(P??0.)lowercollagencontentintheLVofeplerenone‐treatedvs.untreatedCVB3‐infectedmiceatDays8and28,respectively.Thisresultedinanearlyandlong‐lastingimprovementofLVdimensionandfunction,asindicatedbyreducedLVend‐systolicvolumeandend‐diastolicvolume,andanincreaseinLVcontractility(dP/dtmax)andLVrelaxation(dP/dtmin),respectively(P??0.05).SWR/J小鼠感染5×个CVB3菌斑形成单位（南希株），从第1天开始每天用依普利酮（毫克/千克体重）或安慰剂治疗。在感染后第8天或第28天，对小鼠进行血流动力学特征分析，随后处死小鼠进行免疫组织学和分子生物学分析。依普利酮对CVB3负荷无影响。在第8天，左心室细胞间粘附分子1表达、单核细胞/巨噬细胞、氧化应激和凋亡分别降低了1.8倍（P0.05）、1.4倍（P0.05）、3.2倍（P0.01）和2.1倍（P0.），在依普利酮治疗组和未治疗组CVB3感染小鼠中观察到。在体外，依普利酮使CVB3诱导的心肌细胞氧化应激和凋亡减少了1.4倍（P0.01）和1.2倍（P0.01）。此外，用依普利酮处理的培养基和未经处理的CVB3感染的HL-1心肌细胞培养基培养的心脏成纤维细胞的胶原生成量减少了1.1倍（P0.05）。这些改善在体内转化为心脏纤维化的预防，如依普利酮治疗和未治疗CVB3感染小鼠在第8天和第28天分别降低了1.4倍（P0.01）和2.1倍（P0.）。如左室收缩末期容积和舒张末期容积减少，左室收缩性（dP/dtmax）和舒张末期舒张功能（dP/dtmin）分别增加（P0.05），这导致了左心室尺寸和功能的早期和长期改善。ConclusionsEarlyinterventionwiththeMRAeplerenonemodulatestheacutehostanddefencereactionandpreventscardiacdiseaseprogressioninexperimentalCVB3‐inducedmyocarditiswithoutaggravationofviralload.Thefindingsadvocateforaninitiationoftherapyofviralmyocarditisasearlyaspossible,evenbeforetheonsetofinflammation‐inducedmyocardialdysfunction.Thismayalsohaveimplicationsforcoronavirusdisease‐19therapy.在实验性CVB3诱导的心肌炎中，早期使用MRA依普利酮干预可调节急性宿主和防御反应，并防止心脏疾病的进展，而不会加重病毒载量。该研究结果主张尽早开始病毒性心肌炎的治疗，甚至在炎症引起的心肌功能障碍开始之前。这也可能对冠状病毒病-19治疗产生影响。IntroductionMyocarditisismost
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