ROLE OF NEUTROPHILS IN RADICAL PRODUCTION DURING ISCHEMIA AND REPERFUSION OF THE RAT-BRAIN - EFFECT OF NEUTROPHIL DEPLETION ON EXTRACELLULAR ASCORBYL RADICAL FORMATION
ROLE OF NEUTROPHILS IN RADICAL PRODUCTION DURING ISCHEMIA AND REPERFUSION OF THE RAT-BRAIN - EFFECT OF NEUTROPHIL DEPLETION ON EXTRACELLULAR ASCORBYL RADICAL FORMATION
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DOI：
10.1038/jcbfm.1995.119
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发表时间：
1995-11-01
影响因子：
6.3
通讯作者：
KOGURE, K
中科院分区：
文献类型：
--
作者：
MATSUO, Y;KIHARA, T;KOGURE, K
越来越多的实验数据表明，氧自由基可能参与了脑缺血再灌注损伤。氧自由基的一个潜在来源是激活的中性粒细胞，为了研究中性粒细胞在脑缺血再灌流过程中产生自由基的作用，我们观察了抗中性粒细胞单抗(RP3)去除循环中的中性粒细胞对大脑中动脉(MCA)闭塞1h后自由基形成的影响。在本研究中，我们使用了一种新的电子自旋共振方法与脑微透析相结合。该方法使用内源性抗坏血酸自由基(AR)浓度作为氧自由基的标志，并且不需要自旋捕捉剂，在载体对照组中，在MCA闭塞期间细胞外AR降低。再灌流后30min和1h，AR显著升高，至2 h恢复至接近基础水平，再灌流后2 4h再次升高。在用RP3处理的大鼠中，在大脑中动脉闭塞时AR下降的程度与赋形剂对照组相同。而RP3可完全抑制再灌流后细胞外AR的增加。在整个实验期间，RP3处理对细胞外抗坏血酸或组织Po-2的变化没有影响。结论：中性粒细胞是局灶性脑缺血再灌流过程中氧自由基的主要来源。
A growing body of experimental data indicate that oxygen radicals may mediate the brain injury during ischemia-reperfusion. One potential source of oxygen radicals is activated neutrophils, To study the role of neutrophils in radical production during cerebral ischemia-reperfusion, we evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on radical formation in rats with 1-h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents, In the vehicle controls, extracellular AR decreased during MCA occlusion. After reperfusion, AR significantly increased at 30 min and 1 h, returned to near basal level until 2 h, and increased again at 24 h after reperfusion. In the rats treated with RP3, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, RP3 treatment completely inhibited the increase in extracellular AR after reperfusion. RP3 treatment exerted no effect on the changes in extracellular ascorbate or tissue Po-2, throughout the experimental period. In conclusion, neutrophils are a major source of oxygen radicals during reperfusion after focal cerebral ischemia.