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多胺通过调节线粒体通透性转换孔在心肌缺血再灌注损伤中发挥双重作用

陈慧颖, 贾晓丽, 赵淑琴, 郑卫红, 梅志刚, 杨红卫, 张世忠^*

三峡大学医学院生理学教研室，宜昌 443002

摘要

多胺(腐胺、亚精胺和精胺)是一类重要的聚阳离子化合物，在哺乳动物各种生理和病理过程中起重要作用。本研究旨在探索多胺(腐胺、亚精胺和精胺)在心肌缺血再灌注(ischemia/reperfusion, I/R)损伤中的作用及其机制。采用Langendorff离体心脏灌流装置对大鼠离体心脏进行灌流，全心缺血30 min，再灌注120 min。在复灌前10 min给予不同浓度的多胺(0.1、1、10、15 μmol/L腐胺、亚精胺和精胺)、环孢菌素A (0.2 μmol/L)或苍术苷(20 μmol/L)。记录血流动力学变化；分光光度法检测灌流液中乳酸脱氢酶(lactate dehydrogenase, LDH)含量；TTC染色法测定心肌梗死面积；分离心肌线粒体，Ca2+诱导肿胀，分光光度计测定线粒体通透性转换孔(mitochondrial permeability transition pore, MPTP)的开放程度。结果显示，与单独的I/R相比，0.1和1 μmol/L多胺处理改善大鼠心脏功能，降低LDH释放，减少心肌梗死面积，但这些作用被MPTP开放剂苍术苷抑制。在分离自正常大鼠的线粒体，0.1和1 μmol/L多胺处理抑制了MPTP的开放。10和15 μmol/L多胺处理却出现相反的作用，这些作用被MPTP抑制剂环孢菌素A抑制。以上结果表明，多胺既可通过抑制MPTP减轻心肌I/R损伤，又可通过促进MPTP开放加重心肌I/R损伤。

关键词： 心脏; 缺血再灌注; 线粒体通透性转换孔; 多胺

分类号：R331

Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore

Chen Hui-ying, Jia Xiao-li, Zhao Shu-qin, Zheng Wei-hong, Mei Zhi-gang, Yang Hong-wei, Zhang Shi-zhong^*

Department of Physiology, College of Medical Science, China Three Gorges University, Yichang 443002, China

Abstract

Polyamines (putrescine, spermidine, and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells. The study was to investigate their role in cardioprotection against ischemia/reperfusion (I/R) injury and the underlying mechanism. Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac I/R was achieved by 30 min of global ischemia followed by 120 min of reperfusion. Different concentrations of polyamines (0.1, 1, 10, and 15 μmol/L of putrescine, spermidine, and spermine), cyclosporin A (0.2 μmol/L), or atractyloside (20 μmol/L) were given 10 min before the onset of reperfusion. The hemodynamics were monitored; the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically; infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method; and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria. The results showed that compared to I/R alone, 0.1 and 1 μmol/L polyamines treatment improved heart function, reduced LDH release, decreased infarct size, and these effects were inhibited by atractyloside (MPTP activator). In isolated mitochondria from normal rats, 0.1 and 1 μmol/L polyamines treatment inhibited MPTP opening. However, 10 and 15 μmol/L polyamines treatment had the opposite effects, and these effects were inhibited by cyclosporin A (MPTP inhibitor). Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.

Key words: Heart; ischemia/reperfusion; mitochondrial permeability transition pore; polyamines

收稿日期：2019-02-25　　录用日期：2019-07-05

通讯作者：张世忠　　E-mail: zhangsz@ctgu.edu.cn

DOI: 10.13294/j.aps.2019.0057

引用本文：

陈慧颖, 贾晓丽, 赵淑琴, 郑卫红, 梅志刚, 杨红卫, 张世忠. 多胺通过调节线粒体通透性转换孔在心肌缺血再灌注损伤中发挥双重作用[J]. 生理学报 2019; 71 (5): 681-688.

Chen Hui-ying, Jia Xiao-li, Zhao Shu-qin, Zheng Wei-hong, Mei Zhi-gang, Yang Hong-wei, Zhang Shi-zhong. Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore. Acta Physiol Sin 2019; 71 (5): 681-688