培哚普利對大鼠心肌缺血-再灌注損傷早期保護機制研究的開題報告

培哚普利對大鼠心肌缺血-再灌注損傷早期保護機制研究的開題報告[Abstract]Heartattackormyocardialinfarctionisacommonheartdiseasethataffectsmillionsofpeopleworldwide.Reperfusiontherapy,suchasthrombolysisandpercutaneouscoronaryintervention,isthemosteffectivetreatmentforacutemyocardialinfarction.However,reperfusionitselfcancauseadditionaldamagetothemyocardium,knownasmyocardialischemia-reperfusioninjury.Thus,developingeffectivetherapiestoprotecttheheartfromischemia-reperfusioninjuryisessential.Previousstudieshaveshownthatperindopril,anangiotensin-convertingenzymeinhibitor,exhibitscardioprotectiveeffectsagainstischemia-reperfusioninjuryinanimalmodels.However,theexactmechanismunderlyingperindopril'scardioprotectiveeffectremainsunclear.Inthisstudy,weaimtoinvestigatetheearlyprotectivemechanismofperindoprilagainstmyocardialischemia-reperfusioninjuryinrats.Wewillperformaseriesofexperimentstoevaluatetheeffectsofperindoprilonmyocardialinfarctsize,oxidativestress,andapoptosis.[Background]Ischemicheartdiseaseremainstheleadingcauseofdeathworldwide.Acutemyocardialinfarction,whichaccountsforthemajorityofischemicheartdiseaseevents,iscausedbythesuddenblockageofacoronaryarteryresultinginthedeathofcardiomyocytesduetolackofoxygensupply.Reperfusiontherapyisthemosteffectivetreatmentforacutemyocardialinfarction,asitrestoresbloodflowtotheischemicmyocardialtissue,salvagesischemicmyocardium,andimprovesclinicaloutcomes.However,reperfusionitselfcanleadtomyocardialinjury,knownasischemia-reperfusioninjury,whichmayevenbemoreseverethanischemiaitself.Agrowingbodyofevidencesuggeststhatoxidativestress,inflammation,andapoptosiscontributetomyocardialischemia-reperfusioninjury.Therefore,developingeffectivetherapiestoprotecttheheartfromischemia-reperfusioninjuryisessential.Perindopril,anangiotensin-convertingenzymeinhibitor,hasbeenshowntoexhibitcardioprotectiveeffectsagainstischemia-reperfusioninjuryinanimalmodels.However,theexactmechanismunderlyingperindopril'scardioprotectiveeffectremainsunclear.[ResearchObjectives]Inthisstudy,weaimtoinvestigatetheearlyprotectivemechanismofperindoprilagainstmyocardialischemia-reperfusioninjuryinrats.Specifically,weaimto:1.Evaluatetheeffectsofperindoprilonmyocardialinfarctsizeinaratmodelofmyocardialischemia-reperfusioninjury.2.Evaluatetheeffectsofperindoprilonoxidativestressmarkersinthemyocardium.3.Evaluatetheeffectsofperindoprilonapoptosisinthemyocardium.[ResearchMethods]Animalmodel:Sprague-Dawleyrats(250-300g)willbeusedinthisstudy.Theanimalswillbehousedincageswithfreeaccesstofoodandwaterandkeptunderstandardlaboratoryconditions.Inductionofischemia-reperfusioninjury:Ratswillundergoleftanteriordescendingcoronaryarteryligationfor30minutesfollowedbyreperfusionfor120minutes.Sham-operatedratswillundergothesameprocedurewithoutcoronaryarteryligation.Experimentalgroups:Ratswillberandomlyassignedtooneoffourgroups:Sham-operatedgroup,ischemia-reperfusion+perindoprilgroup,ischemia-reperfusion+vehiclegroup,andperindopril-onlygroup.Perindopriltreatment:Ratsintheischemia-reperfusion+perindoprilgroupwillreceiveperindopril(1mg/kg/day)viagavagefor7dayspriortoinducingischemia-reperfusion.Theperindopril-onlygroupwillreceivethesametreatment.Measurementofinfarctsize:Attheendofthestudy,heartswillbeexcisedandstainedwith1%triphenyltetrazoliumchloride.Infarctsizewillbedeterminedasapercentageoftheriskzone.Measurementofoxidativestress:Superoxidedismutase(SOD),malondialdehyde(MDA),andnitricoxide(NO)willbemeasuredinmyocardialtissue.Measurementofapoptosis:Terminaldeoxynucleotidyltransferase-mediateddUTPnick-endlabeling(TUNEL)assaywillbeusedtoassessmyocardialapoptosis.[ExpectedResults]Weexpectthatperindopriltreatmentwillsignificantlyreduceinfarctsize,oxidativestress,andapoptosisinthemyocardium