瑞舒伐他汀对糖尿病大鼠心肌tgf-β1的表达及心肌纤维化的影响-effect of rosuvastatin on myocardial tgf - β 1 expression and myocardial fibrosis in diabetic rats.docxVIP

瑞舒伐他汀对糖尿病大鼠心肌tgf-β1的表达及心肌纤维化的影响-effect of rosuvastatin on myocardial tgf - β 1 expression and myocardial fibrosis in diabetic rats.docx

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瑞舒伐他汀对糖尿病大鼠心肌tgf-β1的表达及心肌纤维化的影响-effect of rosuvastatin on myocardial tgf - β 1 expression and myocardial fibrosis in diabetic rats

ObjectiveInvestigatetheeffectsofRosuvastatinontheexpressionofTGF-β1andcardiacfibrosisthroughstreptozotocin(STZ)-induceddiabeticratsandprobeintothemechanismofventricularremodelingandcardiacfunctionindiabeticcardiomyopathy.MethodsTwenty-sevenmodelratsofdiabeteswereestablishedbystreptozotocin(STZ)intraperitonealinjection,50mg/kg,whichwererandomlydividedintothreegroups,modelgroup(Model,n=9),Low-doserosuvastatingroup(Ros-L,n=9)andhighdoserosuvastatingroup(Ros-H,n=9).Andanothercontrolgroup(Nomal,n=10)wasalsoestablished.Interventiongroupandcontrolgroupweregivenrosuvastatin2mg/kg/d,5mg/kg/dorally.Thenormalgroupandinterventiongroupwerefedwithsamesalinedaily.Allratswerefedwithnormaldiet.After10weeks,thelevelsofglycosylatedhemoglobin(HbA1c),creatinephosphokinaseisoenzyme(CK-MB),plasmabrainnatriureticpeptide(BNP)andleftventricularmassindex(LVWI)weremeasured.AftermyocardialMassonstained,myocardialcollagenvolumefraction(CVF)wascalculated.ThelevelsofmyocardialTGF-β1mRNAandproteinexpressionweredeterminedbyReal-timePCRandWesternBlot.ResultInadditiontothenormalgroup,HbA1clevelswerenosignificantdifferenceamongthemodelgroups(P0.05).Comparedwithnormalgroup,LVWIofhighdosesofrosuvastatin,lowdosesofrosuvastatinandCK-MBoflowdosegroupweresignificantlyincreased(P0.01).LVWIofhigh-doserosuvastatin,low-dosegroupweresignificantlylowerthaninmodelCK-MBgroup(P0.05),buttherewasnosignificantdifferencebetweenthehighdoseandthelowdosegroups(P0.05).Comparedwiththenormalgroup,BNP,myocardialcollagenvolumefraction,mRNAandproteinexpressionlevelsofTGF-β1ofmodelgroup,highdosesgroup,thelowdosegroupwassignificantlyhigher(P0.01),andhigh-dosegroup,low-dosegroupweresignificantlylowerthanmodelgroup(P0.05).Andmoreoverthereweresignificantdifferencebetweenhighdoseandlowdosegroup(P0.05)。ConclusionRosuvastatindose-dependentdiabeticratscanreducetheexpressionofTGF-β1inthemyocardium,whichcaninhibittheformationofcollagenandmyocardialfibrosis.Thepossiblemechanismscouldbedecreasingtheremodelingofventricular.Thismaybelikelytopro

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