肾髓质PGE2及肾素受体在糖尿病肾病和高血压中的作用PPT医学课件ppt学习课件.ppt

InteractionbetweenRenalMedullaryPGE2and(P)RRinDiabeticNephropathyandHypertension,TianxinYang1,2andWeidongWang11InstituteofHypertension,SunYat-senUniversitySchoolofMedicine;2DepartmentofInternalMedicine,UniversityofUtah,PrevalenceofCKD,CDC2010,IncidentRateofESRD,NIDDK2010,ESRDCosts,NIDDK2010,Diabetes,Hypertension,Glomerulonephritis,PKD,Kidneystones,Drugs,RAS,Proteinuria,Podocytedamage,DiabetesMellitusandDiabeticNephropathy,Nearly26millionAmericanshavediabetes,accordingtonewestimatesfromtheCentersforDiseaseControlandPrevention(CDC).Inaddition,anestimated79millionU.S.adultshaveprediabetes,aconditioninwhichbloodsugarlevelsarehigherthannormal,butnothighenoughtobediagnosedasdiabetes.Prediabetesraisesapersonsriskoftype2diabetes,heartdiseaseandstroke.Diabetesaffects8.3percentofAmericansofallages,and11.3percentofadultsaged20andolder,accordingtotheNationalDiabetesFactSheetfor2011.About27percentofthosewithdiabetes7millionAmericansdonotknowtheyhavethedisease.Prediabetesaffects35percentofadultsaged20andolder.,NationalDiabetesFactSheetfor2011,CDC,AnnualNumber(inThousands)ofNewCasesofDiagnosedDiabetesAmongAdultsAged1879Years,UnitedStates,19802010From1980through2010,thenumberofadultsintheUnitedStatesaged1879withnewlydiagnoseddiabetesmorethantripledfrom493,000in1980toover1.7millionin2010.Thenumberofnewcasesofdiabeteshasincreasedsincetheearly1990s.From2008through2010,thenumberofnewcasesofdiagnoseddiabeteshasshownlittlechange.,NationalDiabetesFactSheetfor2011,CDC,Number(inMillions)ofCivilian,NoninstitutionalizedAdultswithDiagnosedDiabetes,UnitedStates,19802010From1980through2010,thenumberofU.S.adultsaged18yearsorolderwithdiagnoseddiabeteshasmorethantripled(from5.5millionto20.7million).,NationalDiabetesFactSheetfor2011,CDC,Theoverallprevalencesoftotaldiabetes(previouslydiagnosedpluspreviouslyundiagnoseddiabetes)andprediabeteswere9.7%and15.5%,respectively.,Inthemultivariable,multinomial,logitmodels,malesex,olderage,afamilyhistoryofdiabetes,overweight,obesity,centralobesity,increasedheartrate,elevatedsystolicbloodpressure,elevatedserumtriglyceridelevel,educationallevelbelowcollege,andurbanresidencewereallsignificantlyassociatedwithanincreasedriskofdiabetesandprediabetes.,YangetalNEngJMed2010,EpidemiologyDiabeticnephropathyisthemostcommoncauseofchronickidneyfailureandend-stagekidneydiseaseintheUnitedStates,accountingfor44%ofallnewcasesofkidneyfailureintheUnitedStatesin2008.Peoplewithbothtype1andtype2diabetesareatrisk.Theriskishigherifblood-glucoselevelsarepoorlycontrolled.Furthermore,oncenephropathydevelops,thegreatestrateofprogressionisseeninpatientswithpoorcontroloftheirbloodpressure.Alsopeoplewithhighcholesterollevelintheirbloodhavemuchmoreriskthanothers.,糖尿病肾病在西方国家是导致慢性肾病和终末期肾病的最主要病因，在我们国家主要病因仍为原发性肾小球疾病，但糖尿病肾病的发病率有逐年增高的趋势。,以肾小球病变为特征的糖尿病肾病大约在糖尿病诊断之后15至20年出现，病程呈进展性,大约1/3的糖尿病病人有肾脏受累,糖尿病肾病,Diabeticnephropathy,alsoknownasnodulardiabeticglomerulosclerosisandintercapillaryglomerulonephritis,isaprogressivekidneydiseasecausedbyangiopathyofcapillariesinthekidneyglomeruli.Itischaracterizedbynephroticsyndromeanddiffuseglomerulosclerosis.Itisduetolongstandingdiabetesmellitus,andisaprimeindicationfordialysisinmanyWesterncountries.,(Pro)reninReceptorandDiabeticNephropathy,图1.肾素-血管紧张素系统与糖尿病肾病的治疗策略,.,RAS,(Pro)ReninReceptor(PRR)：ANewComponentoftheRAS,BatenburgWW,JanDanserAH.EurJPharmacol.2008May118.Review.,SystemicRAS,SchematicpresentationofthemainstepsintheRAAScascadeandsitesofactionoftheRAASinhibitors,(Pro)reninReceptorandHypertension,CollectingDuctReninSystem,AngII,膜磷脂,花生四烯酸,ProstanoidSynthesisPathway,mPGES-1,AngIIStmulates(P)RRExpressioninPrimaryRatIMCDCells,AngIIStimulatesCOX-2ExpressioninPrimaryRatIMCDCells,Control,AngII(4hr),AngII(12hr),AngII(8hr),43kDa,COX-2,P0.05,PRRProteinExpressioninIMCDCellsafter12HoursofAngIITreatmentwithorwithoutNS-398,AngII,P0.05,P0.01,PRR,43kDa,AngII+NS-398,Vehicle,MediumReninActivity,P0.05,P0.05,EffectofExogenousPGE2onPRRExpression,ExogenousPGE2ReversestheEffectofNS-398,EffectsofStructurallyDistinctEP4Antagonists,43kDa,43kDa,SummaryofResultswith3EPAntagonists,AngII,EffectofEP4AgonistonPRRExpression,CTR,CAY10598,RoleofcAMP-PKAPathwayinControlofBaselinePRRProteinExpressioninIMCDCells,CTR,H89,CTR,Forskolin,43kDa,43kDa,PRR,PRR,PRRProteinExpressioninRatRenalMedullaafter2-WeeksofAngIIinfusionwithorwithoutCelecoxib,AngII+Coxib,PRR,-Actin,Circulatory,RenalRegional,andUrinaryReninActivityandTotalReninContent,P0.05,P0.05,SystolicBloodPressure,CelecoxibAttenuatesAlbuminuriainAngII-InfusedM