The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice  

作　　者：Yuan HONG Wei YAN Sheng CHEN Chong-ran SUN Jian-min ZHANG 

机构地区：[1]Department of Neurosurgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China

出　　处：《Acta Pharmacologica Sinica》2010年第11期1421-1430,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was funded by the Research Fund for the Doctoral Program of Higher Education of China （Grant No 0090101120118） and Zhejiang Provincial Natural Science Foundation in China （Grant No Y2090098）.

摘　　要：Aim： To determine whether Nrf2 signaling pathway activation could attenuate oxidative stress and neuronal damage following trauma- tic brain injury （TBI）. Methods： Controlled cortical impact （CCI） injury was performed in Sprague-Dawley rats and Nrf2-knockout or control mice. Sul- foraphane （SFN）, a potent Nrf2 activator, was used to activate Nrf2. Oxidative stress, lesion volume, neuron degeneration, and neu- rologic dysfunction were determined using biochemical, histopathological and neuroethologic approaches. Protein and mRNA levels of Nrf2 and the antioxidant enzymes heme oxygenase 1 （HO-1） and NAD（P）H：quinine oxidoreductase 1 （NQ01） were assessed using Western blot analysis and RT-PCR. Results： Activation of Nrf2 by SFN（ 5 mp=/＇kg, ip） induced the nuclear translocation and activation of Nrf2, which resulted in an up-reg- ulation of Nrf2-dependent antioxidant enzymes and a reduction of oxidative damage after TBI. In accordance with these biochemical changes, SFN also significantly reduced neuronal death, contusion volume, and neurological dysfunction after TBI. Furthermore, Nrf2- knockout mice showed more severe oxidative stress and neurologic deficits after TBI and did not benefit from the effects of SFN. Conclusion： Nrf2 plays a pivotal role in cell defenses against the oxidative stress of TBI. In addition, pharmacological activation of the Nrf2 signaling pathway by small molecule inducers such as SFN attenuated oxidative stress and neuronal damage following TBI.Aim： To determine whether Nrf2 signaling pathway activation could attenuate oxidative stress and neuronal damage following trauma- tic brain injury （TBI）. Methods： Controlled cortical impact （CCI） injury was performed in Sprague-Dawley rats and Nrf2-knockout or control mice. Sul- foraphane （SFN）, a potent Nrf2 activator, was used to activate Nrf2. Oxidative stress, lesion volume, neuron degeneration, and neu- rologic dysfunction were determined using biochemical, histopathological and neuroethologic approaches. Protein and mRNA levels of Nrf2 and the antioxidant enzymes heme oxygenase 1 （HO-1） and NAD（P）H：quinine oxidoreductase 1 （NQ01） were assessed using Western blot analysis and RT-PCR. Results： Activation of Nrf2 by SFN（ 5 mp=/＇kg, ip） induced the nuclear translocation and activation of Nrf2, which resulted in an up-reg- ulation of Nrf2-dependent antioxidant enzymes and a reduction of oxidative damage after TBI. In accordance with these biochemical changes, SFN also significantly reduced neuronal death, contusion volume, and neurological dysfunction after TBI. Furthermore, Nrf2- knockout mice showed more severe oxidative stress and neurologic deficits after TBI and did not benefit from the effects of SFN. Conclusion： Nrf2 plays a pivotal role in cell defenses against the oxidative stress of TBI. In addition, pharmacological activation of the Nrf2 signaling pathway by small molecule inducers such as SFN attenuated oxidative stress and neuronal damage following TBI.

关 键 词：nuclear factor-erythroid 2-related factor 2 SULFORAPHANE traumatic brain injury oxidative stress heme oxygenase 1 NAD（P） H：quinine oxidoreductase 1 neurological dysfunction 

分 类 号：Q257[生物学—细胞生物学] TP24[自动化与计算机技术—检测技术与自动化装置]