Lu Xin-Yu, Wang Han-Dong, Xu Jian-Guo, Ding Ke, Li Tao
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Cell Mol Neurobiol. 2015 Jul;35(5):713-21. doi: 10.1007/s10571-015-0167-9. Epub 2015 Mar 3.
Traumatic brain injury (TBI) is a worldwide public health and medical problem. Oxidative stress is recognized as an important contributing factor in the pathogenesis of TBI. The present study was designed to explore the anti-oxidative effect of Nuclear factor erythroid 2-related factor 2 (Nrf2) on brain damage induced by traumatic injury in a mouse model. Moderate weight-drop impact head injury was induced in adult male mice. The mice were randomly divided into four groups: Nrf2(+/+) sham-operation, Nrf2(-/-) sham-operation, Nrf2(+/+) TBI, and Nrf2(-/-) TBI group. Neurological scores were evaluated 24 h after TBI, followed by collection of the brain specimens. Brain edema was detected by the wet-dry ratio method. The expression of NOX2 protein in the brain specimen was investigated using Western Blot analysis and immunohistochemical staining. In addition, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were evaluated in the brain tissues. Twenty-four hours after TBI, our results showed Nrf2(+/+) TBI mice have more severe neurological deficits and brain edema than Nrf2(+/+) sham group. On the other hand, the Nrf2(-/-) TBI mice were found to have significantly increased neurological deficits and brain edema, compared to Nrf2(+/+) TBI mice (P < 0.05). At the same time, we found that the expression of NOX2 protein, MDA level were significantly increased in Nrf2(-/-) mice, while SOD activity was considerably decreased after TBI compared to Nrf2(+/+) mice (P < 0.05). We demonstrated that deletion of Nrf2 exacerbates brain injury after TBI in mice, suggesting that Nrf2 may play an important role in protecting brain injury after TBI, possibly by modulating oxidative stress.
创伤性脑损伤（TBI）是一个全球性的公共卫生和医学问题。氧化应激被认为是TBI发病机制中的一个重要促成因素。本研究旨在探讨核因子红细胞2相关因子2（Nrf2）对小鼠创伤性脑损伤诱导的脑损伤的抗氧化作用。对成年雄性小鼠进行中度重量落体撞击头部损伤。将小鼠随机分为四组：Nrf2(+/+)假手术组、Nrf2(-/-)假手术组、Nrf2(+/+)TBI组和Nrf2(-/-)TBI组。在TBI后24小时评估神经学评分，随后收集脑标本。采用干湿比法检测脑水肿。使用蛋白质免疫印迹分析和免疫组织化学染色研究脑标本中NOX2蛋白的表达。此外，评估脑组织中的丙二醛（MDA）水平和超氧化物歧化酶（SOD）活性。TBI后24小时，我们的结果显示，与Nrf2(+/+)假手术组相比，Nrf2(+/+)TBI小鼠有更严重的神经功能缺损和脑水肿。另一方面，与Nrf2(+/+)TBI小鼠相比，Nrf2(-/-)TBI小鼠的神经功能缺损和脑水肿明显增加（P < 0.05）。同时，我们发现与Nrf2(+/+)小鼠相比，TBI后Nrf2(-/-)小鼠中NOX2蛋白的表达、MDA水平显著增加，而SOD活性显著降低（P < 0.05）。我们证明，Nrf2的缺失会加剧小鼠TBI后的脑损伤，这表明Nrf2可能在保护TBI后脑损伤中起重要作用，可能是通过调节氧化应激来实现的。
