A型肉毒毒素对电场刺激及SP引发的胃离体平滑肌收缩作用及机理研究的开题报告Title:TheMechanismofActionofTypeABotulinumToxinonElectricalStimulationandSubstanceP-inducedContractionofIsolatedGastricSmoothMuscleIntroduction:Botulinumtoxin(BTX)isaneurotoxinproducedbythebacteriumClostridiumbotulinum.TypeAbotulinumtoxin(BTX-A)iscommonlyusedinclinicalpracticetotreatavarietyofdisorders,includingspasticity,hyperhidrosis,andfacialwrinkles.Recently,BTX-Ahasdemonstratedpotentialinthetreatmentofgastrointestinaldisorders,includinggastroparesis,achalasia,andirritablebowelsyndrome.However,themechanismsbywhichBTX-Aexertsitseffectsongastrointestinalsmoothmuscleremainpoorlyunderstood.Objectives:TheaimofthisstudyistoinvestigatetheeffectsofBTX-Aonelectricalfieldstimulation(EFS)andSubstanceP-inducedcontractionofisolatedgastricsmoothmuscle.ThestudywillalsoelucidatetheunderlyingmechanismsofBTX-Aactionongastricsmoothmuscle.Methods:Isolatedgastricsmoothmusclestripswillbeobtainedfromratsandmountedonaforcetransducer.ThestripswillbeexposedtoincreasingconcentrationsofBTX-AandsubjectedtoEFSandSubstancePstimulation.TheforceofcontractionwillbemeasuredandcomparedtocontrolstripsnottreatedwithBTX-A.ThemechanismsofactionofBTX-Awillbeinvestigatedbymeasuringchangesinintracellularcalciumlevels,cyclicadenosinemonophosphate(cAMP)levels,andproteinkinaseC(PKC)activity.Expectedoutcomes:WeexpectthatBTX-Awilldose-dependentlyreduceEFSandSubstanceP-inducedcontractioninisolatedgastricsmoothmuscle.Wealsoexpecttoobservechangesinintracellularcalciumlevels,cAMPlevels,andPKCactivity,revealingtheunderlyingmechanismsofBTX-Aaction.Importance:UnderstandingthemechanismsbywhichBTX-Aexertsitseffectsongastricsmoothmusclewillcontributetothedevelopmentofnewtreatmentsandtherapiesforgastrointestinaldisorders.ThisstudywillalsoprovideinsightsintothepotentialusesofBTX-Ainthetreatmentofothersmoothmuscledisorders.