Sims N R, Williams V K, Zaidan E, Powell J A
Department of Medical Biochemistry and Centre for Neuroscience, School of Medicine, Flinders University, GPO Box 2100, Adelaide, South Australia, Australia.
Brain Res Mol Brain Res. 1998 Oct 1;60(2):141-9. doi: 10.1016/s0169-328x(98)00172-7.
This study evaluated changes in the antioxidant defences of mitochondria induced by 30 min of forebrain ischemia and recirculation up to 24 h in rats. Following treatment, mitochondria were isolated from two brain subregions: the dorsolateral striatum, an area in which there is loss of most neurons, and the paramedian cortex in which most neurons are resistant to damage. During ischemia and the first few hours of recirculation, the mitochondrial defences were largely preserved based on measurements of the activities of the enzymes, superoxide dismutase, glutathione peroxidase and glutathione reductase, as well as the response of the mitochondria to a subsequent exposure to H2O2 in vitro. However, some moderate changes were detected, particularly in the mitochondria from the dorsolateral striatum. A decrease of 30% in the activity of superoxide dismutase was seen at the conclusion of the ischemic period and a small increase in susceptibility to changes induced by H2O2 was detected during early recirculation. This latter change preceded and possibly contributed to the development of an impairment of respiratory function detected in mitochondria from the dorsolateral striatum at 3 h of recirculation. At 24 h of recirculation, larger changes were seen in the activities of all three of the enzymes in mitochondria from the dorsolateral striatum but not the paramedian cortex that was associated with progression to advanced neuronal damage in the former subregion.
本研究评估了大鼠前脑缺血30分钟及再灌注长达24小时所诱导的线粒体抗氧化防御的变化。处理后，从两个脑区分离出线粒体：背外侧纹状体，该区域大多数神经元会丢失；旁正中皮质，其中大多数神经元对损伤具有抗性。在缺血期间及再灌注的最初几个小时，基于超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性测量，以及线粒体对随后体外暴露于过氧化氢的反应，线粒体防御在很大程度上得以保留。然而，检测到了一些适度的变化，特别是在背外侧纹状体的线粒体中。在缺血期结束时，超氧化物歧化酶活性下降了30%，并且在再灌注早期检测到对过氧化氢诱导变化的敏感性略有增加。后一种变化先于并可能导致了在再灌注3小时时背外侧纹状体线粒体中检测到的呼吸功能损害的发展。在再灌注24小时时，背外侧纹状体线粒体中所有三种酶的活性出现了更大的变化，而旁正中皮质的线粒体中则没有，这与前一个脑区中晚期神经元损伤的进展相关。
