Clofibrate PPARα Activation Reduces Oxidative Stress and Improves Ultrastructure and Ventricular Hemodynamics in No-flow Myocardial Ischemia
Clofibrate PPARα Activation Reduces Oxidative Stress and Improves Ultrastructure and Ventricular Hemodynamics in No-flow Myocardial Ischemia
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DOI：
10.1097/fjc.0b013e31826216ed
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发表时间：
2012-10-01
影响因子：
3
通讯作者：
Sanchez-Mendoza, Alicia
中科院分区：
文献类型：
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作者：
Ibarra-Lara, Luz;Hong, Enrique;Sanchez-Mendoza, Alicia
过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）在能量平衡、炎症和心血管功能保护中发挥重要的生理作用。我们评估了氯贝酸诱导的过氧化物酶体增殖物激活受体α（PPAR α）刺激对缺血心肌的抗氧化作用，对心肌形态学和血流动力学的影响。将雄性Wistar大鼠（300 g）分为以下组：（1）假手术组，（2）心肌缺血赋形剂治疗组（MI-V），和（3）心肌缺血氯贝特[100 mg/kg/腹腔内]治疗组（MI-C）。活性氧（ROS）和脂质过氧化增加MI-V，而氯贝特阻止这种影响。过氧化物酶体增殖物激活受体α刺激后，超氧化物歧化酶（SOD）-1和SOD-2表达增加4倍。SOD-1，SOD-2，和过氧化氢酶活性也增加，在响应氯贝特。MI-C组eNOS mRNA和四氢生物蝶呤表达增加。氯贝特能够降低血管紧张素II（AngII）、AngII AT（1）受体，而Ang-（1-7）和AngII AT（2）受体表达增加。心肌形态学和心功能的评估表明，氯贝丁酯改善组织学特征和血流动力学参数。我们的研究结果表明，通过氯贝特刺激过氧化物酶体增殖体激活物激活物α增加抗氧化防御，从而改善心脏功能。
Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPAR alpha) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPAR alpha stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT(1)-receptor, whereas Ang-(1-7) and AngII AT(2)-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPAR alpha stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.