PPARγ配体罗格列酮对大鼠扩张型心肌病的疗效及可能机制

The effect of proliferator-activated receptor-γ agonist on dilated cardiomyopathy rats and its mechanism

目的: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2.0 mg.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3.0 mg.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:DCM组与CON组相比左室射血分数(LVEF),+dp/dtm ax,-dp/dtm ax,TAOC显著降低(P<0.05)。心肌中TNF-,αIL-1,βIL-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-,αIL-1,βIL-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。

Objective： To observe the effect of administration peroxisome proliferator-activated receptor- γagonist Rosiglitazone on dilated cardiomyopathy （DCM）rats induced by adriamycin and its mechanism. Methods： Thirty male Sprague-Dawley rats were randomly divided into 3 groups as follows. 1 ） the control group （CON, n = 10）：The same dose of normal sodium was administered by daily gavage. 2）the dilated cardiomyopathy group （ DcM, n = 6） ： Adriamycin was administered intraperitoneally for 8 weeks. 3 ） the dilated cardiomyopathy ＋ Rosiglitazone group （ DCM ＋ RSG, n = 6）. concomitant adriamycin and rosiglitazone, rosiglitazone administered daily gavage at a dose of 3mg · kg^-1 · d^-1 for 12 weeks. The concentration of TNF-α, IL-6 ,IL-1β ,TAOC, MDA in myocardium were obtained at 15 weeks after treatment. The cardiac function was assessed by echocardiography, hemodynamics at the same time. Results. To compare the DCM group with the CON group, significantly decrease of left ventricular ejection fraction （ LVEF）, ＋ dp/dt -dp/dtmax and TAOC was observed（P 〈0.05）, while the concentration of TNF-α, IL-1β, IL-6, MDA in myocardium, collagen volume fraction （CVF） were all significantly increased （ P 〈 0.05 ）. LVEF, TAOC were improved （ P 〈 0.05 ） by rosiglitazone treatment. Concentration of TNF-α, IL-1β, IL-6, MDA in myocardium and CVF were decreased （ P 〈 0.05 ） by rosiglitazone treatment. Conclusion： Proliferator activated receptor-γagonist rosiglitazone can improve cardiac function in a rat model of dilated cardiomyopathy induced by adriamycin, and the anti-inflammatory, anti-oxidative stress might be two of the mechanisms.