Karibe H, Chen S F, Zarow G J, Gafni J, Graham S H, Chan P H, Weinstein P R
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.
Brain Res. 1994 Jun 27;649(1-2):12-8. doi: 10.1016/0006-8993(94)91043-x.
Oxidative damage by free radicals has been proposed as a mechanism of cerebral injury due to ischemia and reperfusion. Hypothermia protects against ischemic necrosis; however, its effect on oxidative stress has not been investigated. In this study, the effects of hypothermia on oxidative stress were studied by determining consumption of endogenous antioxidants after temporary focal ischemia in rats. Thirty-two Sprague-Dawley rats anesthetized with 1.5% isoflurane underwent 3 h of middle cerebral artery occlusion under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions followed by 3 h of normothermic reperfusion. In the first study (n = 8 per group), intraischemic hypothermia suppressed the reduction of tissue concentrations of endogenous antioxidants, ascorbate (P < or = 0.05), and glutathione (P < or = 0.05) in ischemic cortex but not in caudoputamen. In a parallel study (n = 8 per group), hypothermia reduced tissue damage in ischemic frontoparietal cortex (P < or = 0.05), but not in caudoputamen. Laser-Doppler estimates of cortical blood flow showed that intraischemic hypothermia significantly attenuated early postischemic hyperperfusion (P < or = 0.01) and delayed postischemic hypoperfusion (P < or = 0.01). These results demonstrate that intraischemic mild hypothermia reduces oxidative stress and cell injury after prolonged focal ischemia followed by reperfusion. The reduction of oxidative stress by hypothermia may be related indirectly to attenuation of postischemic blood flow changes.
自由基引起的氧化损伤被认为是缺血再灌注导致脑损伤的一种机制。低温可预防缺血性坏死；然而，其对氧化应激的影响尚未得到研究。在本研究中，通过测定大鼠短暂局灶性缺血后内源性抗氧化剂的消耗情况，研究了低温对氧化应激的影响。32只经1.5%异氟醚麻醉的Sprague-Dawley大鼠在低温（33℃）或正常体温（37℃）条件下接受3小时大脑中动脉闭塞，随后进行3小时正常体温再灌注。在第一项研究中（每组n = 8），缺血期间低温抑制了缺血皮质内源性抗氧化剂（抗坏血酸，P≤0.05；谷胱甘肽，P≤0.05）组织浓度的降低，但在尾状壳核中未观察到这种现象。在一项平行研究中（每组n = 8），低温减少了缺血性额顶叶皮质的组织损伤（P≤0.05），但在尾状壳核中未观察到这种现象。激光多普勒血流仪对皮质血流的评估显示，缺血期间低温显著减轻了缺血后早期的高灌注（P≤0.01）并延迟了缺血后低灌注（P≤0.01）。这些结果表明，缺血期间轻度低温可减轻长时间局灶性缺血再灌注后的氧化应激和细胞损伤。低温引起的氧化应激降低可能与缺血后血流变化的减轻间接相关。
