Dănilă Maria D, Privistirescu Andreea I, Mirica Silvia N, Sturza Adrian, Ordodi Valentin, Noveanu Lavinia, Duicu Oana M, Muntean Danina M
a Department of Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy of Timişoara, Timișoara, Romania.
b Center for Translational Research and Systems Medicine, "Victor Babeş" University of Medicine and Pharmacy of Timişoara, Timişoara, Romania.
Can J Physiol Pharmacol. 2015 Sep;93(9):819-25. doi: 10.1139/cjpp-2015-0103. Epub 2015 Jun 30.
Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 μmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection.
单胺氧化酶(MAOs)最近已成为心血管系统中氧化应激的重要线粒体来源。短暂的缺血预处理(IPC)期间活性氧的产生负责再灌注时的心脏保护作用。本研究的目的是评估两种MAO抑制剂(氯吉兰和帕吉林)对离体大鼠心脏中IPC相关保护作用的影响。将经历30分钟全心缺血和120分钟再灌注的动物分为以下几组:(i)对照组,无额外干预;(ii)IPC组,在指数缺血前进行3个循环的5分钟缺血和5分钟再灌注;(iii)IPC-氯吉兰组,IPC方案前后各用氯吉兰(50μmol/L)处理5分钟;(iv)IPC-帕吉林组,IPC方案前后各用帕吉林(0.5mmol/L)处理5分钟。通过左心室舒张末压(LVDP)以及收缩性(+dLVP/dt max)和舒张性(-dLVP/dt max)指标评估缺血后功能恢复情况。通过TTC染色对梗死面积(IS)进行定量。在两种性别中,IPC均显著改善了功能恢复,在氯吉兰或帕吉林存在的情况下进一步增强。无论是否存在MAO抑制剂,所有预处理组的IS减少情况相当。在离体大鼠心脏中,急性抑制MAOs可增强IPC诱导的缺血后功能恢复,而不干扰抗坏死保护作用。