慢性脑低灌注对小鼠认知功能的影响及其机制研究  

Effects of chronic cerebral hypoperfusion on cognitive function in mice and its molecular mechanism

作　　者：张倩[1] 文婷婷 张振涛[1] 张兆辉[1] Zhang Qian;Wen Tingting;Zhang Zhentao(Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区：[1]武汉大学人民医院神经内科Ⅰ科,430060

出　　处：《卒中与神经疾病》2023年第3期289-293,共5页Stroke and Nervous Diseases

基　　金：纤维蛋白通过诱导tau蛋白聚集介导卒中后认知功能障碍的机制研究(8207050623)

摘　　要：目的 探讨慢性脑低灌注对小鼠认知功能的影响及其可能作用机制。方法 分别准备24只雄性Tau基因敲除(Tau knockout, Tau-KO)小鼠和野生型(Wild-type, WT)小鼠,随机分为4组(n=12):Tau-KO假手术组(Tau-KO Sham)、Tau-KO慢性脑低灌注模型组(Tau-KO chronic cerebral hypoperfusion, Tau-KO CCH)、WT假手术组(WT Sham)和WT慢性脑低灌注模型组(WT CCH),采用双侧颈总动脉置入血管剪切应力调节器方法制备慢性脑低灌注模型,10周后Morris水迷宫检测4组小鼠学习记忆能力,免疫荧光和免疫组化检测Tau蛋白磷酸化(Tau phosphorylation, p-Tau)及纤维蛋白原(Fibrinogen, Fg)的表达水平。结果 慢性脑低灌注可上调p-Tau和Fg的表达并加剧小鼠认知功能障碍,而阻断Tau蛋白后Fg表达减少且小鼠认知功能得到明显改善。结论 慢性脑低灌注可增加p-Tau蛋白及Fg表达,两者协同作用于小鼠认知功能的损伤,而阻断Tau蛋白后小鼠认知功能障碍得到改善。Objective To investigate the effect of chronic cerebral hypoperfusion on cognitive function in mice and the molecular mechanism.Methods 24 male Tau knockout(Tau-KO)mice and wild-type(WT)mice were respectively prepared and randomly divided into 4 groups(n=12):Tau-KO sham operation group(Tau-KO Sham),Tau-KO chronic cerebral hypoperfusion model group(Tau-KO CCH),WT sham operation group(WT Sham)and WT chronic cerebral hypoperfusion model group(WT CCH),and the chronic cerebral hypoperfusion was prepared by bilateral common carotid artery implanted vascular shear-stress regulator.After 10 weeks,we use Morris water maze to test the learning and memory abilities of 4 groups of mice,and the expression levels of tau phosphorylation(p-Tau)and fibrinogen(Fg)was detected by immunofluorescence and immunohistochemistry.Results Chronic cerebral hypoperfusion could upregulate the expression levels of p-Tau and Fg,and aggravate cognitive impairment in mice,while Fg expression was reduced and cognitive function was significantly improved after blocking Tau protein.Conclusion Chronic cerebral hypoperfusion can increase the expression of p-Tau and Fg,which synergistically affect the impairment of cognitive function in mice,and the cognitive impairment of mice is improved after blocking Tau protein.

关 键 词：慢性脑低灌注 TAU蛋白 纤维蛋白原 认知功能 血管性认知功能障碍 

分 类 号：R743.9[医药卫生—神经病学与精神病学]