Ver Donck L, Van Reempts J, Vandeplassche G, Borgers M
Department of Cardiovascular Pathophysiology, Janssen Research Foundation, Beerse, Belgium.
J Mol Cell Cardiol. 1988 Sep;20(9):811-23. doi: 10.1016/s0022-2828(88)80006-3.
It has been proposed that oxygen derived free radicals contribute to reperfusion injury in ischemic tissue: radical induced lipid peroxidation is believed to cause membrane destruction, eventually evolving to cell death. A method is introduced which investigates the effect of exogenously generated reactive O2 species on isolated Ca2+-tolerant rat cardiomyocytes. Singlet oxygen (O2(1)), generated by photo-excitation of the photosensitive dye rose bengal, induced the transformation of elongated rod-shaped cells into hypercontracted rounded cardiomyocytes. These shape changes were prevented by removal of extracellular Ca2+ or by addition of radical scavengers. Pre-treatment with various classes of Ca2+-antagonists dose-dependently reduced the number of hypercontracted cardiomyocytes after exposure to O2(1). Compounds not active on the slow Ca2+-channel (e.g. flunarizine-like) provided a better degree of protection than the genuine slow Ca2+-channel blockers (e.g. dihydropyridines). Ultrastructurally, cardiomyocytes exposed to O2(1) showed a loss of cytochemically demonstrable sarcolemma-associated Ca2+ and the presence of clustered Ca2+-deposits in the mitochondria. Drug pre-treated cells displayed a Ca2+-distribution pattern comparable to unchallenged control cells.
有人提出，缺血组织中的再灌注损伤与氧衍生的自由基有关：自由基诱导的脂质过氧化被认为会导致膜破坏，最终发展为细胞死亡。本文介绍了一种研究外源性产生的活性氧对分离的耐钙大鼠心肌细胞影响的方法。通过对光敏染料孟加拉玫瑰红进行光激发产生的单线态氧（O2(1)）可诱导细长的杆状细胞转变为过度收缩的圆形心肌细胞。去除细胞外钙或添加自由基清除剂可防止这些形态变化。用各类钙拮抗剂预处理可剂量依赖性地减少暴露于O2(1)后过度收缩的心肌细胞数量。对慢钙通道无活性的化合物（如氟桂利嗪类）比真正的慢钙通道阻滞剂（如二氢吡啶类）提供了更好的保护程度。超微结构上，暴露于O2(1)的心肌细胞显示细胞化学可证实的与肌膜相关的钙丢失，以及线粒体中聚集的钙沉积物。药物预处理的细胞显示出与未受挑战的对照细胞相当的钙分布模式。
