免疫介导心脏疾病新策略

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1、NewStrategiesforImmune-mediatedHeartDiseasesMitsuakiIsobeDepartmentofCardiovascularMedicineTokyoMedicalandDentalUniversityChina-JapanCardiovascularForum2008Immune-mediatedheartdiseasesIschemia-reperfusioninjuryAtherosclerosisRestenosisCardiacallograftrejectionCardiacallograftvasculopathyMyocarditi

2、sCongestiveheartfailureArrhythmiaImmune-mediatedheartdiseasesIschemia-reperfusioninjuryAtherosclerosisRestenosisCardiacallograftrejectionCardiacallograftvasculopathyMyocarditisCongestiveheartfailureArrhythmiaInflammationincoronaryarteriosclerosisandatherogenesisPPARγ(Peroxisomeproliferator-activat

3、edreceptor-γ)NFκBAcutecardiacallograftrejectionEctopichearttransplantionrecipients:C3H/Hedonors:BALB/cfullmismatchAdministrationofpioglitazone(3mg/kg/day)totherecipientmice.MurinehearttransplantationSurvivalRatePostoperativeDaysPioglitazone(3mg/kg/day)ControlchowProlongationofheartgraftbypioglitaz

4、one10.80.60.40.2010203040506070**p<0.05Kosuge,Suzuki,Isobe:Circulation113:2613-2622、20060.80.60.40.20OpticalDensityRR+Pio10-6MR+SR+S+Pio10-6MR+S+Pio10-7MR+S+Pio10-5MR:responder(recipient)S:stimulator(donor)Pio:pioglitazone***p<0.05SuppressionofTcellProliferationbyPioglitazoneinMixedLymphocyteReact

5、ion*ChroniccardiacrejectionGraftarterialdisease(GAD)RCALADLCX8-y-oboySmallarteriesMyocardiumAcceleratedcoronarysclerosisGraftvasculopathyCardiacallograftvasculopathyPathology:DiffuseintimalthickeningofsmalltolargecoronaryarteriesPathology:DiffuseintimalthickeningofsmalltolargecoronaryarteriesRiskf

6、actors:CMVinfectionepisodesofacuterejectionRiskfactors:CMVinfectionepisodesofacuterejectionTherapy:?Therapy:?Progression:monthstoyearsProgression:monthstoyearsChroniccardiacallograftrejectionCardiacallograftvasculopathyrecipients:C57BL/6donors:Bm12classIImismatch-10714212835424956dayssacrificeCont

7、rolchowPioglitazone(3mg/kg/day)Telmisartan(10mg/kg/day)8WeeksafterTransplantationLuminalocclusion(%)p<0.05ControlPioglitazoneAttenuationofGraftArteriosclerosisbyTreatmentwithPioglitazoneorTelmisartanControlPiogli