非诺贝特对压力超负荷中期大鼠心肌能量代谢和心室重构的影响  

Effect of Fenofibrate on Myocardial Energy Metabolism and Ventricular Remodeling in Metaphase Pressure Overloaded Rats

作　　者：何燕[1] 邬江涛[1] 钟国强[1] 吴龙飞[1] 李醒三[1] 王炎 陈卓宏[1] 闭奇[1] 

机构地区：[1]广西医科大学第一附属医院老年心内科,广西壮族自治区南宁市530021

出　　处：《中国循环杂志》2013年第2期140-143,共4页Chinese Circulation Journal

基　　金：广西壮族自治区科技厅青年基金项目资助(桂科青0728064);"广西大型仪器协作共用网资助"项目编号:635-2008-048

摘　　要：目的 :研究非诺贝特对压力超负荷中期大鼠心肌能量代谢和心室重构的影响。方法 :采用腹主动脉缩窄术建立Wistar大鼠压力超负荷模型,随机分为对照组(14只)和非诺贝特组(14只);另建立假手术组(14只)。假手术组和对照组给予生理盐水、非诺贝特组给予非诺贝特150 mg/(kg.d),干预8周后,留取大鼠心肌,光镜观察心肌结构,计算胶原容积分数;电镜观察线粒体结构,进行Flameng评分;测定血清及心肌游离脂肪酸水平;蛋白质印迹法、逆转录聚合酶链反应检测过氧化物酶体增殖物激活受体α(PPARα)、中链脂酰辅酶A脱氢酶(MCAD)、肌型肉碱棕榈酰转移酶-1(MCPT-1)蛋白及基因表达。结果 :①干预后,对照组、非诺贝特组心肌左心室质量指数、胶原容积分数较假手术组增高,非诺贝特组则较对照组明显降低(P均<0.05);②干预后,对照组、非诺贝特组心肌线粒体损伤Flameng评分高于假手术组,非诺贝特组评分低于对照组(P均<0.05);③干预后,非诺贝特组血清及心肌游离脂肪酸较对照组明显降低(P均<0.05);④干预后对照组、非诺贝特组心肌PPARα、MCPT-1、MCAD蛋白及基因表达均较假手术组下调,非诺贝特组较对照组上调(P均<0.05),差异均有统计学意义。结论 :在压力超负荷中期,非诺贝特通过上调大鼠心肌PPARα、MCPT-1、MCAD基因表达,增强脂肪酸氧化,而降低血清和心肌游离脂肪酸,减轻线粒体损伤,减轻左心室肥厚和心肌纤维化,有助于保护压力超负荷下大鼠心脏功能。Objective： To investigate the effect of fenofibrate on myocardial energy metabolism and ventricular remodeling in metaphase pressure overloaded rats. Methods： The metaphase pressure overloaded animal model was established by aortic constriction in wistar rats and then randomly divided them into 3 groups, Control group and Sham operation （Sham） groupand the rats received normal saline in both groups, and Medication group, the rats received fenofibrate 150mg/（kg.d）. n=14 in each group, all animals were treated for 8 weeks. The rats＇ myocardial structure was observed by light microscope and the collagen volume fraction was calculated. The mitochondrial structure was studied by electron microscope and the Flameng score for myocardial mitochondrial injury was calculated. Serum and myocardial free fatty acid levels were examined, PPAR α, MCAD and MCPT-1 gene and protein expressions were assessed by RT-PCR and western blot analysis respectively. Result： ① Compared with Sham group, both Control and Medication groups presented increased left ventricular weight index and collagen volume fraction; Medication group was much lower than that in Control group, P〈0.05. （~） Compared with Sham group, both Control and Medication groups showed increased Flameng score; Medication group was lower than that in Control group, P〈0.05. ② The serum and cardiac free fatty acid level in Medication group was lower than Control group, P〈0.05.③ The expression of PPAR α, MCPT-1 and MCAD in both Control and Medication groups were down-regulated than that in Sham group; they were up-regulated in Medication group than that in Control group, P〈0.05. Conclusion： Fenofibrate could increase fatty acid oxidation through up-regulating the expression of PPAR α, MCPT-1 andMCAD, and therefore, reducing the serum and cardiac free fatty acid levels, extenuate mitochondrial injury, those are helpful to protect the cardiac function in metaphase of pressure overload rats.

关 键 词：非诺贝特 肥厚 重构 能量代谢 压力超负荷 

分 类 号：R541[医药卫生—心血管疾病]