SIRT1通过调节氧化应激参与老年COPD大鼠心脏损伤的机制研究的开题报告.docxVIP

SIRT1通过调节氧化应激参与老年COPD大鼠心脏损伤的机制研究的开题报告

Title:

InvestigatingtheMechanismsofSIRT1-mediatedCardiacInjuryinAgedCOPDRatsthroughOxidativeStressRegulation

Background:

Chronicobstructivepulmonarydisease(COPD)isacommonrespiratorydiseasethataffectsthelungsandisoftenassociatedwithcardiovascularcomplications.ItiswellknownthatoxidativestressisacriticalfactorinthepathogenesisofCOPDandcardiovasculardisease.SIRT1,amemberofthesirtuinfamilyofNAD+dependentenzymes,hasbeenshowntoexertprotectiveeffectsagainstoxidativestressandage-relateddiseases.However,theprecisemechanismunderlyingSIRT1-mediatedcardiacinjuryinagedCOPDratsremainselusive.

Objective:

ToinvestigatetheroleofSIRT1incardiacinjuryofagedCOPDratsthroughregulationofoxidativestressandtoexploretheunderlyingmechanisms.

Methods:

1.Animalmodel:MaleSprague-DawleyratswillbeusedtoestablishtheCOPDmodelthroughcigarettesmokeexposurefor24weeks,andagedrats(18months)willbeselectedforexperiment.

2.Experimentaldesign:

Group1:Controlgroup(normalagedratswithoutexposuretocigarettesmoke)

Group2:COPDgroup(agedratsexposedtocigarettesmoke)

Group3:SIRT1activatorgroup(agedCOPDratstreatedwithSRT1720,aSIRT1activator)

Group4:SIRT1inhibitorgroup(agedCOPDratstreatedwithEX527,aSIRT1inhibitor)

3.Measurementofoxidativestressmarkers:Thelevelsofoxidativestressmarkers,includingmalondialdehyde(MDA),superoxidedismutase(SOD),andglutathioneperoxidase(GPx),willbemeasuredusingcommercialkits.

4.Westernblotanalysis:WesternblotanalysiswillbeusedtodetecttheexpressionlevelsofSIRT1,NF-κB,andHO-1incardiactissues.

5.Histologicalanalysis:Hematoxylinandeosin(HE)stainingwillbeusedtoanalyzecardiacstructure,whileMassonstrichromestainingwillbeusedtoassessthedegreeofmyocardialfibrosis.

ExpectedOutcome:

1.Thelevelsofoxi