Department of Pharmacology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
J Cardiovasc Pharmacol. 2012 Oct;60(4):323-34. doi: 10.1097/FJC.0b013e31826216ed.
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 (PPARα) 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 PPARα 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 AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.
过氧化物酶体增殖物激活受体 (PPAR) 在能量平衡、炎症和心血管功能保护中发挥着关键的生理作用。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 (PPARα) 刺激对缺血心肌的抗氧化作用对心肌形态和血液动力学的影响。雄性 Wistar 大鼠 (300g) 分为以下几组：(1)Sham，(2)心肌缺血 vehicle 处理组 (MI-V)，和 (3)心肌缺血氯贝酸 [100mg/kg/腹腔内)处理组 (MI-C)。在 MI-V 组中，活性氧 (ROS) 和脂质过氧化增加，而氯贝酸则阻止了这种作用。PPARα 刺激使超氧化物歧化酶 (SOD)-1 和 SOD-2 的表达增加了 4 倍。SOD-1、SOD-2 和过氧化氢酶的活性也随着氯贝酸的增加而增加。MI-C 组的 eNOS mRNA 和四氢生物蝶呤增加。氯贝酸能够降低血管紧张素 II (AngII)、AngII AT1 受体，而 Ang-(1-7) 和 AngII AT2 受体的表达增加。对心肌形态和心脏功能的评估表明，氯贝酸改善了组织学特征和血液动力学参数。我们的结果表明，氯贝酸对 PPARα 的刺激增加了抗氧化防御，从而改善了心脏功能。
