Institute of Emergency and Critical Care Medicine, National Yang-Ming University, and Department of Emergency, Taipei Veterans General Hospital, Taipei, Taiwan ROC.
Am J Emerg Med. 2012 Mar;30(3):405-11. doi: 10.1016/j.ajem.2010.12.025. Epub 2011 Feb 5.
We investigated the correlation of proinflammatory transcript nuclear factor κB (NF-κB) and antioxidative gene transcript nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in peripheral blood mononuclear cells (PBMCs) with the tumor necrosis factor α (TNF-α) response after endotoxin stimulation and the clinical outcome of severely injured patients.
Thirty-two severe blunt trauma patients (injury severity score>16) with systemic inflammatory response syndrome were enrolled. Age- and sex-matched healthy persons were the controls. Patients' blood samples were obtained at 24 and 72 hours after injury. Peripheral blood mononuclear cells were isolated, and measurements for NF-κB p65 translocation, Nrf2 and phosphorylated inhibitory κB-α expressions, and TNF-α levels were assayed after endotoxin stimulation.
In the trauma patients, TNF-α hyporesponse, depressed NF-κB p65 translocation, and phosphorylated inhibitory κB-α expression in PBMCs were found at 24 and 72 hours after injury; the Nrf2 expressions in PBMCs were not significantly different between patients and controls. The TNF-α levels had significant correlation with the NF-κB translocation and the trend of negative correlation with Nrf2 expression. Fifteen patients had critical injury (injury severity score≥25). Patients with critical injury had a lower NF-κB signal and a lower TNF-α response than did the counter group. Twelve patients developed organ failure; their Nrf2 expressions were significantly lower than those of patients without organ failure.
The endotoxin hyporesponse associated with NF-κB and Nrf2 signal alternations in PBMCs of injured patients develops early after injury. The hyporesponse of PBMCs with a lower TNF-α level correlates with a lower NF-κB signal and is associated with critical injury, whereas a depressed Nrf2 expression in PBMCs is associated with later organ failure in trauma patients.
我们研究了外周血单个核细胞（PBMC）中促炎转录核因子κB（NF-κB）和抗氧化基因转录核因子-红细胞 2 相关因子 2（Nrf2）的表达与内毒素刺激后肿瘤坏死因子α（TNF-α）反应以及严重创伤患者的临床转归之间的相关性。
纳入 32 例全身炎症反应综合征的严重钝性创伤患者（损伤严重程度评分>16）。年龄和性别匹配的健康人为对照组。患者在损伤后 24 小时和 72 小时采血。分离外周血单个核细胞，在脂多糖刺激后检测 NF-κB p65易位、Nrf2 和磷酸化抑制κB-α表达以及 TNF-α水平。
在创伤患者中，在损伤后 24 小时和 72 小时发现 PBMC 中 TNF-α低反应、NF-κB p65易位和磷酸化抑制κB-α表达受抑制；PBMC 中 Nrf2 的表达在患者与对照组之间无显著差异。TNF-α水平与 NF-κB 易位呈显著相关，与 Nrf2 表达呈负相关趋势。15 例患者发生严重损伤（损伤严重程度评分≥25）。严重损伤患者的 NF-κB 信号较低，TNF-α反应较低。12 例患者发生器官衰竭；他们的 Nrf2 表达明显低于无器官衰竭的患者。
创伤患者 PBMC 中与 NF-κB 和 Nrf2 信号改变相关的内毒素低反应在损伤后早期发生。PBMC 对 TNF-α水平较低的低反应与 NF-κB 信号较低有关，与严重损伤有关，而 PBMC 中 Nrf2 表达的降低与创伤患者后期的器官衰竭有关。
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