Nrf2在氢气治疗脊髓缺血再灌注损伤中的作用及机制

项目名称： Nrf2在氢气治疗脊髓缺血再灌注损伤中的作用及机制

项目编号： No.81200948

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 黄怡

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 脊髓缺血性损伤是胸腹主动脉及脊柱手术后常见并发症之一，严重者可引起脊髓功能障碍，甚至截瘫。我们在国际上首次报道氢气对脊髓缺血再灌注损伤具有显著的保护作用，然而其机制尚未阐明。氢气的保护作用与脊髓抗氧化酶活性升高密切相关，而Nrf2是直接调控抗氧化酶表达的关键分子。预实验发现氢气治疗可提供脊髓Nrf2的表达。因此，我们推测：Nrf2在氢气治疗脊髓缺血再灌注损伤中起重要作用。本项目拟在动物和细胞水平运用行为学、形态学和分子生物学等方法，探讨氢气治疗脊髓缺血再灌注损伤的最佳方案，检测脊髓组织中Nrf2的基因转录、蛋白表达和定位以及核转位活性等变化，进一步观察其下游分子HO-1、GSTs等变化，同时利用相关干预剂，明确Nrf2是否在氢气治疗脊髓缺血再灌注损伤中发挥重要作用，深入探讨氢气神经保护的分子机制，为脊髓缺血性损伤的防护及研制神经保护药物提供新视角。

中文关键词： 脓毒症；七氟醚；氧气；一氧化氮；肺损伤

英文摘要： Spinal cord ischemia is a common complication after the operation of thoraco-abdominal aorta and spinal cord, which can cause spinal cord dysfunction, even paraplegia. We firstly reported that hydrogen gas (H2) had a protective effect against spinal cord ischemia-reperfusion (I/R) damage, however, the mechanism is unclear. The protective role of H2 is significantly associated with the increase of anti-oxidant enzymatic activities, and Nrf2 is the key molecule directly regulating anti-oxidant enzymes. Our preliminary experiment showed that H2 could improve the Nrf2 expression in spinal cord. Therefore, we hypothesized that Nrf2 play an important role in protective effects of hydrogen gas against spinal cord I/R damage. Using the methods of ethology, morphology and molecular biology, this study was designed in vivo and in vitro to investigate: 1) the best treatment protocol of H2 against spinal cord I/R damage; 2) the changes of Nrf2 mRNA and protein, location and nuclear translocation activity in spinal cord tissue, and the expression and activities of downstream target gene (GSTs, HO-1); 3) the protective effects of H2 after using the activator and inhibitor of Nrf2. This study will prove whether Nrf2 play an important role in H2 against spinal cord I/R damage. It will offer new targets for development of neurop

英文关键词： sepsis；sevoflurane；Oxygen；nitric oxide；lung injury