Kurokawa T, Kobayashi H, Nonami T, Harada A, Nakao A, Takagi H
Department of Surgery II, Nagoya University School of Medicine, Tsurumai 65, Showa-ku, Nagoya, 466, Japan.
J Surg Res. 1996 Nov;66(1):1-5. doi: 10.1006/jsre.1996.0363.
The glutathione in mitochondria is thought to play a crucial role in protecting mitochondria against ischemia-reperfusion-induced injury. However, little is known about the mitochondrial redox system. This study was conducted to clarify changes of mitochondrial glutathione redox during liver ischemia and reperfusion and its role on energy producing function. Rats were divided into three groups each of which were treated respectively with saline (Control), buthionine sulfoximine (BSO), which induces a rapid decrease in tissue glutathione concentrations, and gamma-glutamylcysteine ethyl ester (GCE), which conversely induces a rapid increase in tissue glutathione concentrations before induction of ischemia. Liver ischemia was induced for 120 min, and blood reflow was subsequently restored for 60 min. Total and mitochondrial glutathione concentrations, mitochondrial respiratory function, and tissue adenine nucleotide were determined after both the ischemic and the reperfusion periods. In all groups, concentrations of the reduced form of glutathione (GSH) gradually decreased during ischemia and reperfusion. On the other hand, significant increases in mitochondrial GSH were apparent after reperfusion despite significant decreases during ischemia in the control and GCE groups. Total and mitochondrial GSH in the BSO and GCE groups were significantly lower and higher, respectively, compared with the control throughout the experiment. Recovery of the mitochondrial energy producing function and cellular adenine nucleotide after reperfusion were dependent on GSH concentrations. We conclude that mitochondrial GSH concentrations dramatically change in a different manner from cytosolic concentrations after reperfusion, and that recovery of the mitochondrial energy-producing function might be closely associated with mitochondrial GSH concentrations.
线粒体中的谷胱甘肽被认为在保护线粒体免受缺血再灌注损伤方面起着关键作用。然而，人们对线粒体氧化还原系统知之甚少。本研究旨在阐明肝脏缺血和再灌注期间线粒体谷胱甘肽氧化还原的变化及其对能量产生功能的作用。将大鼠分为三组，分别用生理盐水（对照组）、丁硫氨酸亚砜胺（BSO，可使组织谷胱甘肽浓度迅速降低）和γ-谷氨酰半胱氨酸乙酯（GCE，在缺血诱导前可使组织谷胱甘肽浓度迅速升高）进行处理。诱导肝脏缺血120分钟，随后恢复血流60分钟。在缺血期和再灌注期后测定总谷胱甘肽和线粒体谷胱甘肽浓度、线粒体呼吸功能以及组织腺嘌呤核苷酸。在所有组中，缺血和再灌注期间还原型谷胱甘肽（GSH）的浓度逐渐降低。另一方面，尽管对照组和GCE组在缺血期间显著降低，但再灌注后线粒体GSH明显增加。在整个实验过程中，BSO组和GCE组的总谷胱甘肽和线粒体谷胱甘肽分别显著低于和高于对照组。再灌注后线粒体能量产生功能和细胞腺嘌呤核苷酸的恢复取决于谷胱甘肽浓度。我们得出结论，再灌注后线粒体谷胱甘肽浓度与胞质浓度的变化方式不同，线粒体能量产生功能的恢复可能与线粒体谷胱甘肽浓度密切相关。
