Department of Biotechnology, Autonomous Metropolitan University, Iztapalapa Campus, Av. Ferrocarril de San Rafael Atlixco 186, Col. Leyes de Reforma 1ª. Sección, Alcaldía Iztapalapa, Mexico City 09310, Mexico.
Department of Pharmacobiology, Center for Research and Advanced Studies of the National Polytechnic Institute, Calz. de los Tenorios 235, Col Granjas Coapa, Tlalpan, Mexico City 14330, Mexico.
Int J Mol Sci. 2024 Oct 23;25(21):11391. doi: 10.3390/ijms252111391.
Pharmacological preconditioning is an alternative to protect the heart against the consequences of damage from ischemia/reperfusion (I/R). It is based on the administration of specific drugs that imitate the effect of ischemic preconditioning (IPC). Peroxisomal proliferator-activated receptors (PPARs) can prevent apoptosis in pathologies such as I/R and heart failure. Therefore, our objective was to determine if the stimulation of PPARα with fenofibrate (feno) decreases the apoptotic process induced by hypoxia/reoxygenation (HR), high glucose (HG), and HR/HG. For that purpose, cardiomyocyte cultures were divided into the following groups: Group 1-control (Ctrl); Group 2-HR; Group 3-HR + 10 μM feno; Group 4-HG, (25 mM glucose); Group 5-HG + feno; Group 6-HR/HG, and Group 7-HR/HG + feno. Our results indicate that cell viability decreases in neonatal cardiomyocytes undergoing HR, HG, and their combination, while feno improved cell viability. Feno treatment decreased apoptosis compared with HG-, HR-, or HG/HR-vehicle-treated. Nuclear- and mitochondrial-apoptosis markers increased in neonatal cardiomyocytes from HR, HG, and HR/HG; while the cytotoxicity decreased in cells treated with feno. In addition, the expression of Bax, Bad, and caspase 9 decreased due to feno, while 14-3-3ɛ and Bcl2 were increased. Inner mitochondrial cytochrome C increased with feno in every condition, as well as mitochondrial activity. Feno treatment prevented injury in the ultrastructure and in the mitochondrial membranes. Thus, our results suggest that feno decreases apoptosis in neonatal cardiomyocytes, improving the ultrastructure of mitochondria in the pathological conditions studied.
药物预处理是一种保护心脏免受缺血/再灌注（I/R）损伤的替代方法。它基于给予特定的药物，这些药物模拟缺血预处理（IPC）的效果。过氧化物酶体增殖物激活受体（PPARs）可以预防 I/R 和心力衰竭等疾病中的细胞凋亡。因此，我们的目的是确定用非诺贝特（fenofibrate，feno）刺激 PPARα 是否可以减少缺氧/复氧（HR）、高葡萄糖（HG）和 HR/HG 诱导的细胞凋亡过程。为此，将心肌细胞培养物分为以下几组：第 1 组-对照组（Ctrl）；第 2 组-HR；第 3 组-HR+10 μM feno；第 4 组-HG（25 mM 葡萄糖）；第 5 组-HG+feno；第 6 组-HR/HG；第 7 组-HR/HG+feno。我们的结果表明，HR、HG 及其组合作用下的新生心肌细胞活力降低，而 feno 可提高细胞活力。与 HG-、HR-或 HG/HR-载体处理相比，feno 处理可降低细胞凋亡。HR、HG 和 HR/HG 中的新生心肌细胞中的核和线粒体凋亡标志物增加；而用 feno 处理的细胞的细胞毒性降低。此外，由于 feno 的作用，Bax、Bad 和 caspase 9 的表达减少，而 14-3-3ɛ 和 Bcl2 的表达增加。在每种情况下，feno 都会增加细胞内线粒体细胞色素 C 和线粒体活性。feno 处理可防止超微结构和线粒体膜损伤。因此，我们的结果表明，feno 可减少新生心肌细胞中的细胞凋亡，改善研究病理条件下的线粒体超微结构。
