Simvastatin Re-Couples Dysfunctional Endothelial Nitric Oxide Synthase in Experimental Subarachnoid Hemorrhage 英文参考文献.docVIP

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Simvastatin Re-Couples Dysfunctional Endothelial Nitric Oxide Synthase in Experimental Subarachnoid Hemorrhage 英文参考文献.doc

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Simvastatin Re-Couples Dysfunctional Endothelial Nitric Oxide Synthase in Experimental Subarachnoid Hemorrhage 英文参考文献

SimvastatinRe-CouplesDysfunctionalEndothelialNitric OxideSynthaseinExperimentalSubarachnoid Hemorrhage MohammedSabri1,2,3,JingluAi1,2,3,PhilipA.Marsden4,5,R.LochMacdonald1,2,3 * 1DivisionofNeurosurgery,St.Michael’sHospital,Toronto,Ontario,Canada,2LabattFamilyCentreofExcellenceinBrainInjuryandTraumaResearch,KeenanResearch Centre,LiKaShingKnowledgeInstituteofSt.Michael’sHospital,Toronto,Ontario,Canada,3DepartmentofSurgery,UniversityofToronto,Toronto,Ontario,Canada, 4RenalDivision,KeenanResearchCentre,LiKaShingKnowledgeInstituteofSt.Michael’sHospital,Toronto,Ontario,Canada,5DepartmentofMedicine,Universityof Toronto,Toronto,Ontario,Canada Abstract Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage(SAH).WepreviouslyfoundthatthereisincreasedeNOSfunctionafterSAHbutthatitisuncoupled,leadingto secondarycomplicationssuchasvasospasm,microthromboembolismandneuronalapoptosis.Herewetestthehypothesis thatrecouplingeNOSwithsimvastatincanpreventthesecomplications.SAHwascreatedinmicethatweretreatedwith vehicle or simvastatinstarting 2 weeks before or30 minutes after SAH.SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomerformationthatwasassociatedwithSAH,decreasedsuperoxideanionradicalproductionandincreasedNO.These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, micro- thromboemboliandneuronalinjury. Citation:SabriM,AiJ,MarsdenPA,MacdonaldRL(2011)SimvastatinRe-CouplesDysfunctionalEndothelialNitricOxideSynthaseinExperimentalSubarachnoid Hemorrhage.PLoSONE6(2):e17062.doi:10.1371/journal.pone.0017062 Editor:ColinCombs,UniversityofNorthDakota,UnitedStatesofAmerica ReceivedOctober26,2010;AcceptedJanuary14,2011;PublishedFebruary23,2011