Objective: To investigate the effects of nuclear factor erythroid 2-related factor 2 (Nrf2) activator sulforaphane (SFP) on ischemi~reperfusion injury in mice. Methods: The mice were randomly divided into sham group, vehicle group and SFP group. Mice in the vehicle and SFP group were intraperitoneally treated with a vehicle solution or 5 mg/kg SFP immediately after 1 h transient middle cerebral artery occlusion (MCAO). After 1 h MCAO, reperfusion was established by removing the filament under brief general anesthesia. Infarct volume was evaluated by 2, 3, 5-three phenyl tetrazolium chloride staining, and motor deficits were evaluated by neurological score method. Western blotting was employed to determine alternation of Nrf2, heme oxygenase-1 and phospho-nuclear factor kappa B (NF-κB) protein in the ischemic cortex after reperfusion. Results: SFP attenuated the infarct volume and improved neurological deficits 24 h after reperfusion. SFP activated the expression of Nrf2 and heme oxygenase-1 2 h and 6 h after reperfusion respectively. SFP also attenuated the phosphorylation of NF-κB 2 h after reperfusion. Finally, SFP improved the survival rate 7 days after MCAO. Conclusion:The activation of Nrf2 by SFP has a neuroprotective effect mediated by attenuating both oxidative stress and neuroinflammation. SFP is an effective therapeutic candidate for the treatment of ischemia-reperfusion injury.%目的:探讨核因子相关因子2(Nrf2)激动剂莱菔硫烷(SFP)对小鼠脑缺血再灌注损伤(IRI)的影响.方法:将小鼠随机分为Sham组、模型组和SFP组.模型组和SFP组小鼠在短暂性大脑中动脉闭塞(MCAO)后1h腹腔立即注射PBS或SFP(5 mg/kg)溶液.MCAO后1h,在短暂全身麻醉下取出大脑中动脉的线栓,开始再灌.采用2,3,5-氯化三苯基四氮唑染色比较各组小鼠IRI后脑梗死体积;采用神经行为学评分法评估各组小鼠IRI后的神经症状;采用免疫印迹检测模型组和SFP组小鼠IRI后大脑皮质Nrf2、血红素加氧酶-1(HOH)和核转录因子-κB (NF-cB)蛋白的变化情况.结果:SFP治疗可使小鼠再灌24 h后梗死体积和神经功能缺损明显改善.再灌注后2h后,SFP激活Nrf2;再灌注6h后,HO-1激活.再灌注2h后,SFP也降低NF-κB磷酸化水平.SFP提高小鼠MCAO后7d的生存率.结论:通过SFP激活Nrf2可减轻IRI后氧化应激和炎症反应,具有神经保护作用.
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