Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor 英文参考文献.docVIP

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Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor 英文参考文献.doc

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Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor 英文参考文献

AlcoholWorsensAcuteLungInjurybyInhibitingAlveolar SodiumTransportthroughtheAdenosineA1Receptor LauraDada.,AngelR.Gonzalez.,DanielaUrich,SaulSoberanes,TomasS.Manghi,SergioE.Chiarella, NavdeepS.Chandel,G.R.ScottBudinger,Go¨khanM.Mutlu* Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America Abstract Objective:Alcoholintakeincreasestheriskofacutelunginjury(ALI)andtheacuterespiratorydistresssyndrome(ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently availabletotreatordecreasetheriskofARDSinpatientswithalcoholism.Wehaverecentlyshownincreasedlevelsoflung adenosineinhibitalveolarfluidclearance,animportantpredictorofoutcomeinpatientswithARDS.Wehypothesizedthat + alcoholmightworsenlunginjurybyincreasinglungadenosinelevels,resultinginimpairedactiveNa transportinthelung. Methods: We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderatetosevereintoxicationandmeasuredtherateofalveolarfluidclearanceandNa,K-ATPaseexpressioninperipheral lungtissueandassessedtheeffectofalcoholonsurvivalduringexposuretohyperoxia.WeusedprimaryratalveolartypeII + cellstoinvestigatethemechanismsbywhichalcoholregulatesalveolarNa transport. Results:Exposuretoalcoholreducedalveolarfluidclearance,downregulatedNa,K-ATPaseinthelungtissueandworsened hyperoxia-inducedlunginjury.AlcoholcausedanincreaseinBALfluidadenosinelevels.Asimilarincreaseinlungadenosine levelswasobservedafterexposuretohyperoxia.InprimaryratalveolartypeIIcellsalcoholandadenosinedecreasedthe abundanceoftheNa,K-ATPaseatthebasolateralmembraneviaamechanismthatrequiredactivationoftheAMPK. Conclusions: Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increasesinlungadenosinelevelsmayberesponsibleforreductioninalveolarfluidclearanceandassociatedw