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.
Sheng Li Xue Bao. 2019 Oct 25;71(5):681-688.
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 Ca-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.
多胺（腐胺、亚精胺和精胺）是必需的多阳离子，在哺乳动物细胞的各种生理和病理生理过程中发挥重要作用。本研究旨在探讨它们在抗心肌缺血/再灌注（I/R）损伤中的作用及其潜在机制。采用Langendorff灌注法对雄性Sprague-Dawley大鼠的离体心脏进行灌注，通过30分钟全心缺血后再灌注120分钟建立心脏I/R模型。在再灌注开始前10分钟给予不同浓度的多胺（腐胺、亚精胺和精胺分别为0.1、1、10和15 μmol/L）、环孢素A（0.2 μmol/L）或苍术苷（20 μmol/L）。监测血流动力学；用分光光度法测定冠状动脉流出液中乳酸脱氢酶（LDH）水平；用2,3,5-三苯基氯化四氮唑染色法测定梗死面积；用分光光度法通过钙诱导的离体心脏线粒体肿胀来测定线粒体通透性转换孔（MPTP）的开放情况。结果表明，与单纯I/R组相比，0.1和1 μmol/L多胺处理可改善心脏功能、减少LDH释放、减小梗死面积，而这些作用被苍术苷（MPTP激活剂）抑制。在正常大鼠的离体线粒体中，0.1和1 μmol/L多胺处理可抑制MPTP开放。然而，10和15 μmol/L多胺处理则产生相反的作用，且这些作用被环孢素A（MPTP抑制剂）抑制。我们的研究结果表明，多胺可能通过抑制或激活MPTP开放对I/R损伤的心脏产生保护或损伤作用。
