M9, A Novel Region of Amino-Nogo-A, Attenuates Cerebral Ischemic Injury by Inhibiting NADPH Oxidase-Derived Superoxide Production in Mice
M9, A Novel Region of Amino-Nogo-A, Attenuates Cerebral Ischemic Injury by Inhibiting NADPH Oxidase-Derived Superoxide Production in Mice
复制标题
M9 是氨基-Nogo-A 的一个新区域，通过抑制小鼠 NADPH 氧化酶衍生的超氧化物产生来减轻脑缺血损伤
DOI：
10.1111/cns.12083
复制
发表时间：
2013-05-01
影响因子：
5.5
通讯作者：
Xiong, Li-Ze
中科院分区：
文献类型：
--
作者：
Guo, Fan;Jin, Wei-Lin;Xiong, Li-Ze
急性脑卒中时，氧化应激和神经元凋亡导致神经系统损伤。本研究探讨了Nogo-A 290-562残基区（M9）与HIV反式激活因子（达特）蛋白转导结构域的融合是否对脑缺血具有神经保护作用及其机制。方法采用雄性C57 BL/6 J小鼠大脑中动脉闭塞法制备短暂性局灶性脑缺血模型。在再灌注开始时通过腹膜内注射施用TAT-M9、其突变体或载体。观察神经行为学评分、梗死体积、神经细胞凋亡及Bax/Bcl-2比值。丙二醛（MDA），活性氧（ROS）水平，和NADPH氧化酶的激活进行了测量，在存在或不存在的NADPH氧化酶抑制剂夹竹桃苷或激活剂四溴肉桂酸（TBCA）。结果免疫荧光结果证实，TAT-M9可被转导至脑实质内，显著改善神经行为，缩小梗死体积，保护神经细胞免于凋亡，抑制NADPH氧化酶的活化，降低MDA和ROS含量。此外，夹竹桃麻素模仿TAT-M9的有益作用，而TBCA消除它们。结论TAT-M9通过抑制NADPH氧化酶介导的氧化损伤和神经元凋亡减轻小鼠脑缺血。TAT-M9可能是治疗脑血管疾病的潜在药物。
Aims In acute stroke, neurological damage is due to oxidative stress and neuronal apoptotic death. This study investigated whether Nogo-A 290-562 residues region (M9), fused to the transduction domain of the HIV trans-activator (TAT) protein, is neuroprotective against cerebral ischemia and the mechanisms. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in male C57BL/6J mice. TAT-M9, its mutation or vehicle was applied via intraperitoneal injection at the onset of reperfusion. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the ratio of Bax/Bcl-2 were evaluated. Malondialdehyde (MDA), reactive oxygen species (ROS) levels, and NADPH oxidase activation were measured in the presence or absence of the NADPH oxidase inhibitor apocynin or activator tetrabromocinnamic acid (TBCA). Results Immunofluorescence results confirmed that TAT-M9 was transduced into brain parenchyma, and it significantly improved neurological behavior, reduced infarct volumes, protected neuronal cells from apoptosis, inhibited activation of NADPH oxidase, and decreased MDA and ROS contents. Furthermore, apocynin imitated the beneficial effects of TAT-M9, while TBCA abolished them. Conclusions Our results demonstrate that TAT-M9 administration attenuates cerebral ischemia by inhibiting NADPH oxidase-mediated oxidative damage and neuronal apoptosis in mice. TAT-M9 may be a potential treatment for cerebrovascular disease.