摘要
目的探讨睡眠节律紊乱对大鼠记忆能力、超微结构、海马Aβ含量和tau蛋白磷酸化的影响及机制,评价一种非创伤性老年性痴呆大鼠模型的构建方法。方法雄性Wistar大鼠36只,随机均分为正常对照组、弱光组(照度400 lux,24 h持续光照)、强光组(照度800 lux,24 h持续光照),每组12只。光照30 d后,Morris水迷宫检测大鼠空间记忆能力,透射电镜观察海马超微结构的改变,放射免疫法检测海马Aβ含量,免疫组织化学法和Western blot检测海马tau蛋白磷酸化水平。结果与正常对照组比较,弱光组和强光组大鼠寻台潜伏期均显著延长;正常对照组大鼠海马组织超微结构正常;弱光组和强光组大鼠海马组织线粒体肿胀,线粒体嵴模糊或消失,结构破坏;神经突触减少甚至缺失,突触间隙模糊,突触小泡数量减少;海马组织Aβ含量增高,海马CA3区神经纤维tau蛋白磷酸化阳性细胞个数增加,蛋白表达水平增高,差异具有统计学意义(P<0.05)。结论睡眠节律紊乱诱导的老年性痴呆动物模型在一定程度上模拟其发病特点,可以用于Alzheimer’s发病机制及其治疗药物的研究。
Objective To discuss the effects and mechanisms of rat＇s memory,ultrastructure,the content of Aβ and tau hyperphosphorylation in rats＇ hippocampus induced by sleep rhythm disorder,evaluate a method for a non traumatic AD model bulilding. Methods 36 male Wistar rats were divided randomly into three groups（ n = 12） ： normal controls that received 12： 12 hr light-dark cycle; weak light group that received 24 hr continuous illumination（ 400 lux illuminance）; strong light group that received 24 hr continuous illumination（ 800 lux illuminance）. After a illuminate period of 30 days,Morris water maze test was used to measure the spatial memory of rats. Transmission electron microscope（ TEM） was used tocan observe the changes of ultrastructure in hippocampus. Content of Aβ was examined by radioimmunity method,and the level of tau phosphorylation was examined determined by immunohistochemistry and western blot. Results Compared to normal controls,in the weak light and strong light groups,the spatial memory were significantly reduced. The results of TEM showed that the ultrastructure were normal in controls. In weak light and strong light groups,mitochondria were to swell,their spines disappeared and structures were disorganized. The synapses reduced or even missing,synaptic cleft was fuzzy and synaptic vesiclere was thickened. The content of Aβ,the positive cell and expression of tau in rats hippocampus CA3 region were higher（ P〈0. 05）. Conclusion The Alzheimer-like rat induced by sleep rhythm disorder simulated some characteristics of human AD to some extent,it can be usesd to study the pathogenesis and treatment of drug research.
出处
《中风与神经疾病杂志》
CAS
北大核心
2015年第6期497-500,共4页
Journal of Apoplexy and Nervous Diseases
