Nuclear factor-κB activation during cerebral reperfusion:: effect of attenuation with N-acetylcysteine treatment
Nuclear factor-κB activation during cerebral reperfusion:: effect of attenuation with N-acetylcysteine treatment
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DOI：
10.1016/s0169-328x(98)00045-x
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Cheng, C
中科院分区：
文献类型：
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作者：
Carroll, JE;Howard, EF;Cheng, C
我们检测了转录因子核因子-κ B（NF-κ B B）的激活，NF-κ B参与了暂时性大脑中动脉闭塞（TMCAO）后再灌注过程中内皮细胞粘附蛋白的上调。我们假设N-乙酰半胱氨酸（NAC），一种抑制NF-κ B活化的抗氧化剂，将改变脑再灌注损伤的事件。我们使用TMCAO大鼠模型。使左侧大脑缺血2小时，然后使该区域再灌注。动物用NAC（150 mg/kg）或盐水安慰剂处理，处死，并在不同的时间间隔评估左右半球中的活化NF-κ B。还测量了从单独一组动物收集的每个半球的脑梗死体积。活化的NF-κ B B，由p65和p50 Rel蛋白组成，在受影响的半球再灌注后15分钟显著增加。NAC处理后15 min激活完全消失。在闭塞结束前1小时和24小时，NAC治疗使受累半球的梗死体积百分比从35.5 +/- 2.8%（S.E.）至18.1 ± 2.1%（p < 0.01）。在闭塞后1小时（在NF-κ B峰之后）和24小时再次进行NAC治疗也显著地将梗死体积百分比从34.8 +/- 3.8%降低到24.6 +/- 3.8%（p < 0.05）。因此，虽然NAC在再灌注后15分钟抑制NF-κ B B的活化，但药物通过其他未明确的机制减少脑梗死。这些结果提出了问题的各种作用NF-κ B B在脑梗死后再灌注。(C)1998年Elsevier Science B.V.
We examined activation of the transcription factor, nuclear factor-kappa B (NF-kappa B), which participates in the upregulation of endothelial cell adhesion proteins, during reperfusion after temporary middle cerebral artery occlusion (TMCAO). We hypothesized that N-acetylcysteine (NAC), an antioxidant which inhibits NF-kappa B activation, would alter events in brain reperfusion injury. We used a rat model of TMCAO. The left sides of the brains were rendered ischemic for 2 h, and then the area was allowed to reperfuse. The animals were treated with NAC (150 mg/kg) or saline placebo, sacrificed, and activated NF-kappa B was assessed in both the left and right hemispheres, all at varying intervals. Cerebral infarction volume was also measured in each of the hemispheres collected from a separate group of animals. Activated NF-kappa B, consisting of p65 and p50 Rel proteins, was significantly increased 15 min after reperfusion in the affected hemisphere. The activation at 15 min was completely abolished with NAC treatment. NAC treatment 1 h prior to the end of occlusion and at 24 h reduced the percentage infarction volume of the affected hemispheres from 35.5 +/- 2.8% (S.E.) to 18.1 +/- 2.1% (p < 0.01). NAC treatment at 1 h after the occlusion (after the NF-kappa B peak) and again at 24 h also significantly reduced the percentage infarction volume from 34.8 +/- 3.8% to 24.6 +/- 3.8% (p < 0.05). Thus, while NAC inhibited activation of NF-kappa B at 15 min after reperfusion, the drug acted to reduce cerebral infarction by additional, undefined mechanisms. These results bring into question the various roles of NF-kappa B in cerebral infarction followed by reperfusion. (C) 1998 Elsevier Science B.V.