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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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