核因子相关因子-2激动剂莱菔硫烷在小鼠脑缺血再灌注损伤中的神经保护作用

Neuroprotective effects of nuclear factor erythroid 2-related factor 2 activator sulforaphane on cerebral ischemia reperfusion injury in mice

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(5mg/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(HO-1)和核转录因子-κB(NF-κB)蛋白的变化情况。结果:SFP治疗可使小鼠再灌24h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。

Objective： To investigate the effects of nuclear factor erythroid 2-related factor 2 （Nrf2） activator sulforaphane （SFP） on ischemia-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-gB） 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-~B 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.