Xue Yan, Qu Zhenzhen, Fu Jian, Zhen Junli, Wang Wenjing, Cai Yunlei, Wang Weiping
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
Brain Res Bull. 2017 May;131:221-228. doi: 10.1016/j.brainresbull.2017.04.019. Epub 2017 May 4.
Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28days. The results showed that ATX treatment ameliorated learning and memory deficits after repeated cerebral IR. ATX administration rescued the number of surviving pyramidal neurons in the CA1 and CA3 regions. The concentration of malondialdehyde was decreased, and the levels of reduced glutathione and superoxide dismutase in the hippocampus were increased. Electron microphotography revealed that damage to the ultrastructure of neurons was also reduced by ATX administration. In addition, the expression levels of Cytochrome C (Cyt C), cleaved Caspase-3 and Bax were lower and the expression of Bcl-2 was higher compared to control IR mice. Our findings demonstrate that ATX is able to suppresse learning and memory impairment caused by repeated cerebral IR and that this effect is associated with attenuation of oxidative stress.
氧化应激与神经退行性疾病如血管性认知障碍（VCI）的发病机制有关。本研究旨在探讨抗氧化剂虾青素（ATX）在VCI小鼠模型中的潜在神经保护作用。通过反复阻断雄性ICR小鼠双侧颈总动脉诱导VCI，导致反复的脑缺血/再灌注（IR）损伤。手术后，小鼠每天经胃内给予ATX或等体积的赋形剂，持续28天。结果表明，ATX治疗改善了反复脑IR后的学习和记忆缺陷。给予ATX挽救了CA1和CA3区域存活的锥体神经元数量。丙二醛浓度降低，海马中还原型谷胱甘肽和超氧化物歧化酶水平升高。电子显微镜照片显示，给予ATX也减少了神经元超微结构的损伤。此外，与对照IR小鼠相比，细胞色素C（Cyt C）、裂解的Caspase-3和Bax的表达水平较低，而Bcl-2的表达较高。我们的研究结果表明，ATX能够抑制反复脑IR引起的学习和记忆障碍，并且这种作用与氧化应激的减轻有关。
