Araki N, Greenberg J H, Uematsu D, Sladky J T, Reivich M
Department of Neurology, University of Pennsylvania, Philadelphia 19104.
J Cereb Blood Flow Metab. 1992 Jan;12(1):43-52. doi: 10.1038/jcbfm.1992.6.
To clarify the relationship between calcium metabolism and free radical damage during the reperfusion period following ischemia, we investigated the effect of superoxide dismutase (SOD) on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 12 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:500 nm), NADH signal (464 nm), and reflectance (340 nm) during ultraviolet excitation (340 nm) directly from the cortex in vivo. The middle cerebral artery (MCA) was occluded for 1 h; only cats in which the EEG amplitude was depressed to less than 10% of control during the occlusion were entered into the study. Starting 2 min prior to release of the occlusion and continuing for 4 min, SOD (10,000 U/kg) was slowly infused in six cats, while in six cats, the vehicle only was infused. During MCA occlusion, the Ca2+ signal ratio increased significantly in both groups with no significant difference between the groups. During reperfusion, the Ca2+ signal ratio remained at a high level in the vehicle-treated group, while in the SOD-treated group, the Ca2+ signal ratio decreased. There was a statistically significant difference between the two groups at 10, 20, and 30 min after reperfusion (p less than 0.01). The histologically damaged area in the SOD-treated group was significantly smaller than that in the vehicle-treated group (p less than 0.01). These data suggest that the histoprotective action of SOD may be due to its ability to attenuate increases in intracellular calcium during the recirculation period following focal cerebral ischemia.
为了阐明缺血后再灌注期间钙代谢与自由基损伤之间的关系，我们研究了超氧化物歧化酶（SOD）对12只猫局灶性脑缺血再灌注后细胞内游离钙变化、皮质血流量和组织学变化的影响。使用indo-1（一种荧光细胞内Ca2+指示剂），我们在体内直接从皮质在紫外线激发（340nm）期间同时测量了Ca2+信号比率（400:500nm）、NADH信号（464nm）和反射率（340nm）的变化。大脑中动脉（MCA）闭塞1小时；只有在闭塞期间脑电图振幅降低至对照值的10%以下的猫才纳入研究。在闭塞解除前2分钟开始并持续4分钟，给6只猫缓慢输注SOD（10,000U/kg），而给另外6只猫仅输注赋形剂。在MCA闭塞期间，两组的Ca2+信号比率均显著增加，两组之间无显著差异。在再灌注期间，赋形剂治疗组的Ca2+信号比率保持在高水平，而在SOD治疗组中，Ca2+信号比率下降。再灌注后10、20和30分钟两组之间存在统计学显著差异（p<0.01）。SOD治疗组的组织学损伤面积明显小于赋形剂治疗组（p<0.01）。这些数据表明，SOD的组织保护作用可能是由于其在局灶性脑缺血后的再循环期间减弱细胞内钙增加的能力。
