Matsunaga A, Nomura Y, Kuroda S, Tamura M, Nishihira J, Yoshimura N
Biophysics Group, Research Institute for Electronic Science, Hokkaido University, Sapporo 060, Japan.
Am J Physiol. 1998 Oct;275(4):C1022-30. doi: 10.1152/ajpcell.1998.275.4.C1022.
Using the blood-free perfused rat brain, we examined the redox behavior of cytochrome oxidase of two chromophores, heme a + a3 and copper. When perfusate inflow was stopped to induce global ischemia, the reduction of heme a + a3 was triphasic, with a rapid phase, a slow phase, and a second rapid phase. In contrast, the reduction of copper was monophasic after the rapid phase of heme a + a3. The triphasic reduction of heme a + a3 was diminished by energy-depleting treatments, such as addition of an uncoupler. The time course of the reduction of copper was not affected by the energy depletion. During global ischemia the decrease in creatine phosphate nearly paralleled the reduction of heme a + a3, whereas ATP remained at the control level until approximately 60% of heme a + a3 was reduced in the rapid phase. In the slow phase, ATP started to decrease with the reduction of copper. The redox behavior of copper was similar to the slow phase of the reduction of heme a + a3 because of the higher oxygen affinity of copper than of heme a + a3. Therefore, the rapid phase of the reduction of heme a + a3 can be used as an alarm before a decrease in ATP, whereas the reduction of copper indicates a decrease in ATP under severe hypoxia. Thus the copper signal in noninvasive near-infrared spectroscopy is a useful parameter for the clinical setting.
我们使用无血灌注大鼠脑，研究了细胞色素氧化酶中两个发色团（血红素a + a3和铜）的氧化还原行为。当停止灌注液流入以诱导全脑缺血时，血红素a + a3的还原呈三相，包括快速相、缓慢相和第二个快速相。相比之下，在血红素a + a3的快速相之后，铜的还原是单相的。血红素a + a3的三相还原通过能量耗竭处理（如添加解偶联剂）而减弱。铜还原的时间进程不受能量耗竭的影响。在全脑缺血期间，磷酸肌酸的减少几乎与血红素a + a3的还原平行，而ATP在快速相中直到大约60%的血红素a + a3被还原时仍保持在对照水平。在缓慢相中，ATP随着铜的还原开始减少。由于铜比血红素a + a3具有更高的氧亲和力，铜的氧化还原行为类似于血红素a + a3还原的缓慢相。因此，血红素a + a3还原的快速相可在ATP降低之前用作警报，而铜的还原表明在严重缺氧下ATP降低。因此，无创近红外光谱中的铜信号是临床环境中的一个有用参数。
