Wagner K R, Kleinholz M, Myers R E
Medical Research Service, Veterans Administration Medical Center, Cincinnati, OH 45220.
J Neurol Sci. 1990 Dec;100(1-2):142-51. doi: 10.1016/0022-510x(90)90025-i.
Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
暴露于缺氧环境的高血糖猫而非血糖正常的猫在复氧后会出现神经学症状，包括肌束震颤、局灶性和强直阵挛性癫痫发作以及在一段无症状期后出现昏迷。这些有症状的高血糖猫可能会发生脑水肿，并根据存活时间的长短表现出弥漫性神经元损伤或脑梗死。从有症状而非无症状的猫分离出的脑线粒体中，由二磷酸腺苷（ADP）和解偶联剂刺激的氧消耗率降低。由于呼吸功能受损可能是由电子传递链功能改变引起的，我们测量了分离的脑线粒体中细胞色素c、b和aa3的浓度以及五个电子传递复合体的活性。在有症状的猫中，特别是在复合体IV细胞色素氧化酶中存在明显改变，活性降低了57%，辅基（细胞色素aa3）浓度降低了45%。呼吸链其他部分的降低不太明显，分别包括细胞色素c浓度降低27%和电子传递复合体II琥珀酸：泛醌氧化还原酶活性降低41%。细胞色素b浓度以及复合体I、II和V的活性未发生变化。在出现神经学症状之前，缺氧后高血糖猫的线粒体中细胞色素aa3浓度（18%）和细胞色素氧化酶活性（20%）也有小幅但显著的降低。这些结果表明，特定电子传递复合体活性的延迟降低与缺氧后高血糖猫的线粒体呼吸受损和神经功能恶化相关。然而，目前尚不清楚这些缺氧后脑线粒体改变是脑损伤发展过程中的原发性还是继发性事件。
