Jin Wei, Ni Hongbin, Hou Xiaoshan, Ming Xing, Wang Jing, Yuan Baoyu, Zhu Tiansheng, Jiang Jian, Wang Handong, Liang Weibang
Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China; phone: 86 25 83106666;
Ann Clin Lab Sci. 2014 Spring;44(2):151-7.
Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. Three groups were analyzed: a sham group, a SCI group, and a SCI+rhEPO group (n=16 per group). We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by an electrophoretic mobility shift assay (EMSA). We also measured the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay (ELISA); we also measured hindlimb locomotion function by the Basso, Beattie, and Bresnahan (BBB) rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. The results showed that the induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of tBHQ also significantly attenuated SCI induced hindlimb locomotion deficits, spinal cord edema, and apoptosis. To conclude, pre-treatment with tBHQ could attenuate the spinal cord inflammatory response after SCI.
抗氧化转录因子核因子红细胞2相关因子2（Nrf2）在我们之前的研究中已显示在抵御脊髓损伤（SCI）诱导的炎症反应中发挥重要作用。本研究的目的是测试新型Nrf2激活剂叔丁基对苯二酚（tBHQ）是否能保护脊髓免受SCI诱导的炎症损伤。成年雄性Sprague-Dawley大鼠在T8-T9处进行椎板切除术并用血管夹进行压迫。分析了三组：假手术组、SCI组和SCI+rhEPO组（每组n=16）。我们通过电泳迁移率变动分析（EMSA）测量Nrf2和核因子κB（NF-κB）的结合活性。我们还通过酶联免疫吸附测定（ELISA）测量肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的浓度；我们还通过Basso、Beattie和Bresnahan（BBB）评分测量后肢运动功能，通过湿/干重法测量脊髓水肿，并通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）分析测量细胞凋亡。结果表明，tBHQ诱导的Nrf2活性显著降低了损伤脊髓中NF-κB的激活和炎性细胞因子的产生。给予tBHQ还显著减轻了SCI诱导的后肢运动功能障碍、脊髓水肿和细胞凋亡。总之，tBHQ预处理可减轻SCI后的脊髓炎症反应。
