Carroll J E, Howard E F, Hess D C, Wakade C G, Chen Q, Cheng C
Department of Neurology, Medical College of Georgia, Augusta, GA, USA.
Brain Res Mol Brain Res. 1998 May;56(1-2):186-91. doi: 10.1016/s0169-328x(98)00045-x.
We examined activation of the transcription factor, nuclear factor-kappaB (NF-kappaB), 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-kappaB 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-kappaB 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-kappaB, 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-kappaB 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-kappaB 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-kappaB in cerebral infarction followed by reperfusion.
我们研究了转录因子核因子-κB（NF-κB）的激活情况，该因子参与内皮细胞黏附蛋白的上调，研究在大脑中动脉短暂闭塞（TMCAO）后的再灌注过程中进行。我们假设，N-乙酰半胱氨酸（NAC），一种抑制NF-κB激活的抗氧化剂，会改变脑再灌注损伤中的事件。我们使用了TMCAO大鼠模型。将大鼠大脑左侧缺血2小时，然后让该区域再灌注。动物接受NAC（150mg/kg）或生理盐水安慰剂治疗，随后处死，并在不同时间间隔对左右半球中激活的NF-κB进行评估。还测量了从另一组动物收集的每个半球的脑梗死体积。由p65和p50 Rel蛋白组成的激活的NF-κB在再灌注后15分钟时在受影响的半球中显著增加。NAC治疗可完全消除15分钟时的激活。在闭塞结束前1小时和24小时给予NAC治疗，可使受影响半球的梗死体积百分比从35.5±2.8%（标准误）降至18.1±2.1%（p<0.01）。在闭塞后1小时（在NF-κB峰值出现后）和24小时再次给予NAC治疗，也显著降低了梗死体积百分比，从34.8±3.8%降至24.6±3.8%（p<0.05）。因此，虽然NAC在再灌注后15分钟时抑制了NF-κB的激活，但该药物通过其他未明确的机制起到了减少脑梗死的作用。这些结果对NF-κB在脑梗死继以再灌注过程中的各种作用提出了质疑。
