pparγ配体罗格列酮对大鼠扩张型心肌病的疗效及可能机制

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1、PPARγ配体罗格列酮对大鼠扩张型心肌病的疗效及可能机制【摘要】观察PPARγ配体罗格列酮对多柔比星诱导的扩张型心肌病的治疗作用，并探讨可能机制。方法：30只雄性SD大鼠随机分为（1）正常对照组（CON,n=10），等体积生理盐水灌胃；（2）扩张型心肌病组（DCM,n=10），多柔比星2.0mg·kg-1腹腔注射，每周1次，共8周；（3）扩张型心肌病＋罗格列酮组（DCM+RSG,n=10），罗格列酮3.0mg·kg-1·d-1灌胃治疗，共12周。第15周检测心肌相关炎症因子浓度以及总抗氧化能力（TAOC）、丙二醛（MDA）浓度；检测心功能。结果：D

2、CM组与CON组相比左室射血分数（LVEF），+dp/dtmax，-dp/dtmax，TAOC显著降低（P＜0.05）。心肌中TNFα，IL1β，IL6，MDA及胶原容积百分数（CVF）明显升高（P＜0.05），罗格列酮治疗后LVEF，TAOC有所改善（P＜0.05），TNFα，IL1β，IL6，MDA，CVF有所降低（P＜0.05）。结论：PPARγ配体罗格列酮可改善扩张型心肌病大鼠的心功能，其机制可能是提高心肌抗氧化能力、减少炎症因子的释放。【关键词】过氧化物酶体增殖物激活受体γ扩张型心肌病化应激炎症因子［Abstract］Obje

3、ctive:Toobservetheeffectofadministrationperoxisomeproliferatoractivatedreceptorγ15agonistRosiglitazoneondilatedcardiomyopathy(DCM)ratsinducedbyadriamycinanditsmechanism.Methods：ThirtymaleSpragueDawleyratswererandomlydividedinto3groupsasfollows.1)thecontrolgroup(CON,n=10):Th

4、esamedoseofnormalsodiumwasadministeredbydailygavage.2)thedilatedcardiomyopathygroup(DCM,n=6):Adriamycinwasadministeredintraperitoneallyfor8weeks.3)thedilatedcardiomyopathy+Rosiglitazonegroup(DCM+RSG,n=6).concomitantadriamycinandrosiglitazone,rosiglitazoneadministereddailygavag

5、eatadoseof3mg·kg-1·d-1for12weeks.TheconcentrationofTNFα,IL6,IL1β,TAOC,MDAinmyocardiumwereobtainedat15weeksaftertreatment.Thecardiacfunctionwasassessedbyechocardiography,hemodynamicsatthesametime.Results：TocomparetheDCMgroupwiththeCONgroup,significantlydecreaseofleftventricu

6、larejectionfraction(LVEF),+dp/dtmax,-dp/dtmaxandTAOCwasobserved(P＜0.05),whiletheconcentrationofTNFα,IL1β,IL6,MDAinmyocardium,collagenvolumefraction(CVF)wereallsignificantlyincreased(P＜0.05).LVEF,TAOCwereimproved(P＜0.05)byrosiglitazonetreatment.ConcentrationofTNFα,IL1β,IL

7、6,MDAinmyocardiumandCVFweredecreased(P＜0.05)byrosiglitazonetreatment.Conclusion：Proliferatoractivated15receptorγagonistrosiglitazonecanimprovecardiacfunctioninaratmodelofdilatedcardiomyopathyinducedbyadriamycin,andtheantiinflammatory,antioxidativestressmightbetwoofthemechan

8、isms.［Keywords］PPARγ;dilatedcardiomyopathy;oxidativestress;in