Blebbistain, a Myosin II Inhibitor, as a Novel Strategy to Regulate Detrusor Contractility in a Rat Model of Partial Bladder Outlet Obstruction 英文参考文献.docVIP

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Blebbistain, a Myosin II Inhibitor, as a Novel Strategy to Regulate Detrusor Contractility in a Rat Model of Partial Bladder Outlet Obstruction 英文参考文献.doc

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Blebbistain, a Myosin II Inhibitor, as a Novel Strategy to Regulate Detrusor Contractility in a Rat Model of Partial Bladder Outlet Obstruction 英文参考文献

Blebbistain,aMyosinIIInhibitor,asaNovelStrategyto RegulateDetrusorContractilityinaRatModelofPartial BladderOutletObstruction XinhuaZhang1,2,AllenSeftel2,MichaelE.DiSanto1,2* 1DepartmentofUrology,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,UnitedStatesofAmerica,2DepartmentofSurgery/DivisionofUrology,CooperMedical SchoolofRowanUniversity,Camden,NewJersey,UnitedStatesofAmerica Abstract Partialbladderoutletobstruction(PBOO),acommonurologicpathologymostlycausedbybenignprostatichyperplasia,can coexistin40–45%ofpatientswithoveractivebladder(OAB)andisassociatedwithdetrusoroveractivity(DO).PBOOthat induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB) is a myosin II inhibitorwerecentlydemonstratedpotentlyrelaxednormaldetrusorsmoothmuscle(SM)andreportssuggestvariedBLEB efficacyfordifferentSMmyosin(SMM)isoformsand/orSMMvsnonmusclemyosin(NMM).WehypothesizeBLEBinhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model,organbathcontractility,competitiveandReal-Time-RT-PCRwereperformed.Itwasfoundthatobstructed-bladder weightsignificantlyincreased2.74-foldwhileinvitrocontractilityofdetrusortovariousstimuliwasimpaired,50%along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitudebutdepressedfrequency.PBOOswitchedbladderfromaphasic-typetoamoretonic-typeSM.Expressionof5’ myosinheavychain(MHC)alternativelysplicedisoformSM-A(associatedwithtonic-typeSM)increased3-foldwhile3’MHC SM1 and essential light chain isoform MLC17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb) was greatly increased by 4.5-fold. BLEB was found to completelyrelaxdetrusorstripsfrombothsham-operatedandPBOOratspre-contractedwithKCl,carbacholorelectrical fieldstimulationalthoughsensitivitywasslightlydecreased(20%)onlyatlowerdosesfor