Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
J Pharmacol Sci. 2020 Dec;144(4):218-228. doi: 10.1016/j.jphs.2020.09.005. Epub 2020 Sep 18.
Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.
心肌缺血引发一系列病理状态，导致心肌细胞死亡。因此，有必要进行药理学治疗以阻止缺血引起的损伤。贝特类药物已被报道可降低炎症标志物并调节肾素-血管紧张素系统 (RAS)。我们的目的是探讨氯贝特治疗是否能减少心肌梗死后 1 周的心肌损伤。将 Wistar 大鼠分为：1. 假手术或 2. 冠状动脉结扎 (MI)。心肌梗死后 7 天，将大鼠分为接受载体 (V) 或氯贝特 [100mg/kg (C)] 每日治疗 7 天。分析血液样本和左心室。与 MI-V 相比，MI-C 中的 RAS 成分 [血管紧张素 II、血管紧张素转换酶 (ACE) 和 AT 受体] 降低，而 [Ang-(1-7)、缓激肽、ACE-2 和 AT 受体] 对氯贝特治疗呈上升趋势。氧化应激标志物在 MI-V 大鼠中增加，而在 MI-C 大鼠中恢复正常。NO 通路 (Akt、eNOS 和 NO) 在 MI-V 中的参与程度较低，但氯贝特提高了 NO 通路成分及其产生。氯贝特治疗还改善了 MI 引起的纤维化和结构损伤。总之，在心肌梗死后 7 天的大鼠中给予氯贝特可发挥抗氧化、促血管扩张表达谱和抗纤维化作用，表明 PPARα 激活可被视为改善缺血后心脏状况的治疗靶点。
