Mink R B, Dutka A J, Hallenbeck J M
Diving Medicine Department, Naval Medical Research Institute, Bethesda, Md 20814-5055.
Stroke. 1991 May;22(5):660-5. doi: 10.1161/01.str.22.5.660.
The reperfusion of previously ischemic tissue may lead to the formation of highly reactive free radicals that promote tissue injury. Xanthine oxidase has been implicated as one source of these free radicals. We examined the role of xanthine oxidase in brain injury using a cerebrospinal fluid compression model of global cerebral ischemia with 15 minutes of ischemia and 4 hours of reperfusion. Seven dogs were pretreated with the xanthine oxidase inhibitor allopurinol (50 mg/kg for 5 days). Neurophysiological recovery was monitored with cortical somatosensory evoked potentials. As an attempt to correlate brain recovery with the mechanism of protection, free brain malondialdehyde was measured at the end of reperfusion by high-performance liquid chromatography. Brain water content was measured by wet-dry weights. Compared with seven untreated control dogs, allopurinol pretreatment significantly improved recovery of somatosensory evoked potentials after 4 hours of reperfusion. However, the amount of free malondialdehyde in the allopurinol-treated dogs was 32% greater than that in the controls. Brain water content was similar in the two groups. These results suggest that xanthine oxidase contributes to brain injury after ischemia and reperfusion. However, tissue damage caused by xanthine oxidase may be mediated through mechanisms other than free radical production.
先前缺血组织的再灌注可能导致高反应性自由基的形成，从而促进组织损伤。黄嘌呤氧化酶被认为是这些自由基的一个来源。我们使用全脑缺血的脑脊液压迫模型，缺血15分钟，再灌注4小时，研究了黄嘌呤氧化酶在脑损伤中的作用。七只狗用黄嘌呤氧化酶抑制剂别嘌呤醇（50mg/kg，持续5天）进行预处理。用皮层体感诱发电位监测神经生理恢复情况。为了将脑恢复与保护机制相关联，在再灌注结束时通过高效液相色谱法测量脑游离丙二醛。用脑干湿重测量脑含水量。与七只未治疗的对照狗相比，别嘌呤醇预处理显著改善了再灌注4小时后体感诱发电位的恢复。然而，别嘌呤醇治疗组狗的游离丙二醛量比对照组高32%。两组的脑含水量相似。这些结果表明，黄嘌呤氧化酶在缺血再灌注后导致脑损伤。然而，黄嘌呤氧化酶引起的组织损伤可能通过自由基产生以外的机制介导。
