防治高同型半胱氨酸血症的新思路.ppt

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1、ANEWSTRATEGY---TOTREAT/PREVENTEHYPERHOMOCYSTEINEMIAHomocysteine(HCY)isasulfur-containingaminoacidproducedduringcatabolismoftheessentialaminoacidmethionine.HomocysteinemetabolismHYPERHOMOCYSTEINEMIANormalhumanplasmaHCYconcentration5-15μmol/LHyperhomocysteinem

2、ia16-30μmol/L30-100μmol/L>100μmol/LHyperhomocysteinemiaanindependentcardiovascularriskfactorMechanismofCellinjurybyHCYOxidativestressInflammationpathwayEndoplasmicreticulumstressVSMCsover—proliferationInterferelipidmetabolismInterfereendotheliacoagulationact

3、ivitiesInterfereL-arg-NOS/NOpathwayClinicaltherapyandcurrentquestionsVitaminB6,B12andfolicacid—themaintreatmentstrategyIndicationneuraldegenerationEndotheliaprotectionperseBetaineN-athelcysteine,NAC;VitEPeptides----CNP,ADM,CGRPetc.HormoneDrugsTherapeuticNews

4、trategytohyperhomocysteinemiaSulfur-containingaminoacidmetabolismsystem----superregulationfamilyGenerationfromthemethionineIndependentbiologicaleffectsInteractiveregulationandantagonismEndogenousantagonistasanewtherapy/preventionforhyperhomocysteinemia???Tau

5、rineRegulateosmoticpressureStabilizecellmembraneRegulationfreeCa2+InhibitlipidperoxidationRegulateendotheliacontraction/relaxationfactorsynthesize/releaseASanendogenousprotectantinvariousdiseasesincludingcardiovasculardiseasesAntagonismtocardiovascularinjury

6、byHCYEndotheliaInjurystructuredisorderETreleaseLDHreleaseProliferationVSMCsproliferationMyocardiumHCYloweredtautrineconcentrationInhibittaurineuptakeIncreasetaurinereleaseMitochondriaInjuryMethininefoodinducedhyperhomocysteinemiaMyocardialMitochondria(×40000

7、)ControlTaualoneMetaloneMet+TauTaurineantagonismtoHCYcardiovascularinjurybyoxidativestressMitochondriamembraneLipidperoxidationMDAConjugateddieneMyocardialMitochondriaO2-productionandMn-SODactivityMn-SODMyocardialMitochondriaH2O2productionandCATactivityCAT**

8、p<0.01vscontrol;#p<0.05,##p<0.01vsMetMyocyteH2O2productionabMyocyteMitochondriaH2O2productioninvitroMitochondriaO2-productioninvitroSub-mitochondriaH2O2andO2-Mitochondriaenzyme-complex-IIandIIIr