【摘要】 目的研究非诺贝特对慢性心力衰竭(CHF)大鼠心肌能量代谢和心室重构的影响。方法健康雄性Wistar大鼠随机选为假手术组18只;采用腹主动脉缩窄术制备CHF、并成功存活的38只再随机分为对照组20只、非诺贝特组18只[非诺贝特150 mg/(kg·d)],干预10周。计算左心室心肌重构指数、胶原容积分数(CVF)、心肌线粒体损伤程度分级用Flameng评分,免疫印迹法测过氧化物酶体增殖物激活受体α(PPARα)、中链酰基辅酶A脱氢酶(MCAD)、肌型肉碱棕榈酰转移酶1(MCPT 1)蛋白表达,RT-PCR测PPARα、MCAD和MCPT-1mRNA表达。结果与假手术组比较,对照组及非诺贝特组左心室心肌重构指数、CVF和Flameng评分均升高(P<0.05);非诺贝特组左心室心肌重构指数高于对照组、CVF和Flameng评分低于对照组(P<0.05);与假手术组比较,对照组、非诺贝特组心肌PPARα、MCPT-1、MCAD蛋白和基因表达均下调(P<0.05);非诺贝特组表达较对照组上调(P<0.05)。结论非诺贝特通过增强脂肪酸氧化,减轻线粒体损伤,改善心室重构,减轻心肌纤维化。更多还原

【Abstract】 Objective To study the effect of fenofibrate on myocardial metabolism and ventricular remodeling in rats with chronic heart failure(CHF).Methods Eighteen healthy male Wistar rats served as a sham operation group in this study.A CHF model was established by constricting the abdominal artery.Thirty-eight survived rats were rondomly divided into control group(n=20)and fenofibrate group[n=18,fenofibratel50 mg/(kg ? d),for 10 weeks].Left ventricular myocardial remolding index and CVF were culculated.Myocardial mitochondrial injury was scored according to the Flameng scale.Expressions of PPARα,MCAD,MCPT-1 protein and mRNA were detected by Western blot and RT-PCR,respectively.Results The left ventricular myocardial remolding index, CVF and myocardial mitochondrial injury score were significantly higher in control and fenofibrate groups than in sham operation group(P<0.05).The left ventricular myocardial remolding index was significantly higher whereas the CVF and myocardial mitochontia injury score were significantly lower in fenofibrate group than in control group(P<0.05).The expression levels of PPARct,MCPT-1 and MCAD protein were significantly lower in control and fenofibrate groups than in sham operation group and significantly higher in fenofibrate group than in sham operation group(P<0.05).Conclusion Fenofibrate can alleviate mitochondrial injury,improve left ventricular remodeling and reduce myocardiac fibrosis by oxidating fatty acids.更多还原