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The mitochondrial Ca(2+)-activated K(+) channel contributes to cardioprotection by limb remote ischemic preconditioning in rat.

机译:线粒体Ca(2+)激活的K(+)通道有助于大鼠肢体远端缺血预处理对心脏的保护。

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AIMS: To investigate the role of the mitochondrial Ca(2+)-activated K(+) channel in cardioprotection induced by limb remote ischemic preconditioning. MAIN METHODS: Male Sprague-Dawley rats (250-300 g) were randomized into control, ischemia/reperfusion (I/R), remote ischemic preconditioning (RPC), NS1619 (a specific mitochondrial Ca(2+)-activated K(+) channel opener), and RPC+paxilline (a specific mitochondrial Ca(2+)-activated K(+) channel inhibitor) groups. RPC was induced by 4 cycles of 5 min of ligation followed by 5 min of reperfusion of the left femoral artery. Myocardial I/R was achieved by ligation of the left anterior descending coronary artery for 30 min, followed by 120 min of reperfusion. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining, the hemodynamics were monitored, and lactate dehydrogenase (LDH) levels in the coronary effluent, manganese superoxide dismutase (Mn-SOD) content in mitochondria and mitochondrial membrane potential were measured spectrophotometrically. The ultrastructure of cardiomyocyte mitochondria was assessed by electron microscopy. KEY FINDINGS: NS1619 (10 muM) improved heart function, decreased infarct size, reduced LDH release, maintained mitochondrial structural integrity and mitochondrial membrane potential, and increased the mitochondrial content of Mn-SOD to the same degree as RPC treatment. However, paxilline (1 muM) eliminated the cardioprotective effect conferred by RPC. SIGNIFICANCE: The mitochondrial Ca(2+)-activated K(+) channel participates in the myocardial protection by limb remote ischemic preconditioning.
机译:目的:研究线粒体Ca(2+)激活的K(+)通道在肢体远端缺血预处理引起的心脏保护中的作用。主要方法:将雄性Sprague-Dawley大鼠(250-300 g)随机分为对照组,缺血/再灌注(I / R),远程缺血预处理(RPC),NS1619(特定的线粒体Ca(2+)激活的K(+ )通道开放剂)和RPC + paxilline(特定的线粒体Ca(2+)激活的K(+)通道抑制剂)组。结扎5分钟的4个周期,然后再灌注左股动脉5分钟,从而诱发RPC。结扎左冠状动脉前降支30分钟,然后再灌注120分钟,可达到心肌I / R。通过2,3,5-三苯基四唑氯化物染色确定梗塞面积,监测血流动力学,并用分光光度法测定冠状流出物中的乳酸脱氢酶(LDH)水平,线粒体中的锰超氧化物歧化酶(Mn-SOD)含量和线粒体膜电位。 。通过电子显微镜评估心肌细胞线粒体的超微结构。主要发现:NS1619(10μM)改善了心脏功能,减小了梗塞面积,减少了LDH释放,保持了线粒体结构完整性和线粒体膜电位,并使Mn-SOD的线粒体含量增加到与RPC处理相同的程度。但是,paxilline(1μM)消除了RPC赋予的心脏保护作用。意义:线粒体Ca(2+)激活的K(+)通道通过肢体远端缺血预处理来参与心肌保护。

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