依达拉奉激活Nrf2通路减轻脑出血后继发性损伤  

Edaravone attenuate secondary brain injury after intracerebral hemorrhage through activating Nrf2 pathway

作　　者：尚寒冰[1] 胡彦兵 杨德华[3] 张卫峰[1] 赵卫国[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院神经外科,上海200025 [2]喀什地区第二人民医院神经外科,新疆喀什844000 [3]中国科学院上海生命科学研究院上海交通大学医学院健康科学研究所,上海200025

出　　处：《中华神经外科疾病研究杂志》2013年第1期48-51,共4页Chinese Journal of Neurosurgical Disease Research

摘　　要：目的探讨自由基清除剂依达拉奉对大鼠脑出血神经功能与脑水肿的疗效,并通过检测核因子相关因子2(Nrf2)通路及其下游抗氧化酶的表达变化,探索依达拉奉在脑出血中的抗氧化治疗机制。方法采用自体血立体定向注射建立大鼠脑出血模型,依达拉奉干预后24 h分别行神经行为学评分及脑含水量测定,并检测Nrf2通路表达变化,脑组织切片行免疫荧光双标染色,判定Nrf2表达的细胞来源。结果依达拉奉干预脑出血大鼠后24 h,前肢抬起及前肢对称实验较对照组均明显改善,脑含水量亦明显降低。依达拉奉组Nrf2及其下游抗氧化酶血红素加氧酶1(HO-1)、硫氧还蛋白(TRX)、谷胱甘肽-S-转移酶α1(GST-α1)、醌氧化还原酶1(NQO1)转录水平较对照组明显上调,依达拉奉组Nrf2及HO-1蛋白表达较对照组明显升高。脑组织切片免疫荧光双标染色表明,Nrf2主要在神经元中特异性表达。结论依达拉奉可明显减轻大鼠脑出血后神经功能障碍及脑水肿程度,其机制可能与激活内源性抗氧化系统Nrf2通路发挥对神经元的保护作用有关。Objective To investigate the effect of edaravone treatment for attenuating neurologic deficits and brain edema in experimental intracerebral hemorrhage （ICH） rats, and explore the antioxidative mechanism through detecting the activities of nuclear factor erythroid 2-related factor 2 （Nrf2） and downstream antioxidative enzymes. Methods The ICH rat models were established by stereotaxic microinjection of autologous whole blood into the right striatum. The animals were divided into three groups： sham operation, vehicle controls and edaravone treatment. Twenty-four hours after operation, the brain water content and neurological behavior score were evaluated. The expression of Nrf2 pathway was detected by realtime PCR and western bloting at both transcriptional and translational levels. To access the cellular source of Nrf2 expression, double labeling immunofluorescence staining was performed in perihematomal region, Results Systemic administration of edaravone immediately after ICH reduced brain water content and ameliorated the neurologic deficits at 24 h after ICH compared with vehicle. Edaravone also activated Nrt2 pathway and up-regulated antioxidative proteins, such as hemeoxygenase-1 （HO-1）, thioredoxin （TRX）, glatatbione S-transferase-al （GST-cd）, and quinone oxidoreductasel （NQO1）. Double immunofluorescent studies showed that the inununoreactivities of NrI2 were apparently localized in neurons. Conclusion Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. The activation of Nrt2 pathway may play an important role in antioxidative mechanism of edaravone.

关 键 词：脑出血 依达拉奉 核因子相关因子2 氧化应激 继发性脑损伤 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]