Myocardial Autophagy after Severe Burn in Rats 英文参考文献.docVIP

Myocardial Autophagy after Severe Burn in Rats 英文参考文献.doc

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Myocardial Autophagy after Severe Burn in Rats 英文参考文献

MyocardialAutophagyafterSevereBurninRats RongXiao.,MiaoTeng.,QiongZhang,Xiao-huaShi,Yue-shengHuang* InstituteofBurnResearch,StateKeyLaboratoryofTrauma,BurnsandCombinedInjury,SouthwestHospital,TheThirdMilitaryMedicalUniversity,Chongqing,China Abstract Background:Autophagyplaysamajorroleinmyocardialischemiaandhypoxiainjury.Thepresentstudyinvestigatedthe effectsofautophagyoncardiacdysfunctioninratsaftersevereburn. Methods:ProteinexpressionoftheautophagymarkersLC3andBeclin1weredeterminedat0,1,3,6,and12hpost-burnin SpragueDawleyratssubjectedto30%totalbodysurfacearea3rddegreeburns.Autophagic,apoptotic,andoncoticcell death wereevaluatedinthemyocardium ateachtime pointbyimmunofluorescence. Changesof cardiacfunctionwere measuredinaLangendorffmodelofisolatedheartat6hpost-burn,andtheautophagicresponsewasmeasuredfollowing activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI)werealsoappliedtotheexvivoheartmodeltoexaminetherolesofthesefactorsinpost-burncardiacfunction. Results:Autophagiccelldeathwasfirstobservedinthemyocardiumat3hpost-burn,occurringin0.00860.001%oftotal cardiomyocytes,andcontinuedtoincreasetoalevelof0.02260.005%by12hpost-burn.Noautophagiccelldeathwas observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycinenhancedautophagyanddecreasedcardiacfunctioninisolatedhearts6hpost-burn,while3-MAexertedthe oppositeresponse.Enalaprilat,losartan,andDPIallinhibitedautophagyandenhancedheartfunction. Conclusion:Myocardialautophagyisenhancedinsevereburnsandautophagiccelldeathoccurredearlyat3hpost-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important rolesinthisprocessbyregulatingcellsignalingtransduction. Citation: Xiao R, Teng M, Zhang Q, Shi X-h, Huang Y-s

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