氟代柠檬酸对SD大鼠星形胶质细胞的抑制作用及相关机制  

THE INHIBITION EFFECT OF FLUOROCITRATE ON ASTROCYTES OF SD RATS

作　　者：王全保[1] 刘运涌[1] 范新蕾 田茜[1] 李伟[1] 

机构地区：[1]临沂市人民医院神经内科,山东临沂276003 [2]山东医学高等专科学校

出　　处：《山东医学高等专科学校学报》2016年第2期135-138,F0002,共5页Journal of Shandong Medical College

基　　金：临沂市科技发展计划项目(No.201515012)

摘　　要：目的探讨氟代柠檬酸(FC)对脑星形胶质细胞的影响,分析星形胶质细胞是否参与突触蛋白的表达和tau蛋白磷酸化的调控,以期分析阿尔茨海默病的可能发病机制。方法在SD大鼠侧脑室注射1nmol氟代柠檬酸,造成星形胶质细胞三羧酸循环可逆性抑制。采用免疫荧光标记技术;原代海马神经元及星形胶质细胞的培养;western blot检测记忆相关蛋白的水平,如AMPA受体GluR1/2、突触后密度蛋白93/95、Arc、磷酸化的cAMP反应元件相关结合蛋白以及老年痴呆症相关的多个磷酸化位点tau蛋白磷酸化的水平。结果经FC处理可以降低SD大鼠海马神经元记忆相关蛋白水平;通过激活GSK3β或者灭火PP2A活性提高tau蛋白磷酸化的水平。结论 FC对脑星形胶质细胞的功能变化有影响,星形胶质细胞可能参与突触蛋白的表达和tau蛋白磷酸化的调控。Objective To explore the effect of fluorocitrate （FC） on brain astrocytes and to decide wheth- er astrocytes are involved in synaptic protein expressions and tau protein phosphorylation regulation in or- der to find the potential pathogenesis of Alzheimer＇s disease. Methods 1 nmol fluorocitrate was injected into ventricle of SD rats in order to cause reversible inhibition of Krebs cycle in astrocyte. Immunofluorescence labeling technique was performed and primary hippocampal neurons and astrocytes were cultured. Western blot was carried out in order to detect memory-related protein levels, such as the AMPA receptor GluR1/ 2, postsynaptic density protein 93/95, Arc, phosphorylated cAMP response element binding protein and dementia associated plurality of phosphorylation sites of tau protein phosphorylation levels. Results FC treatment reduced the memory associated protein levels in SD rat hippocampal neurons,and the phospho- rylation levels of tau protein can be promoted through activating GSK3β or inhibiting the activity of PP2A.Conclusion FC may affect the functions of cerebral astrocytes, and astrocytes may be involved in the expression of synaptic protein and the regulation of tau protein phosphorylation.

关 键 词：氟代柠檬酸 星形胶质细胞 阿尔茨海默病 

分 类 号：R742[医药卫生—神经病学与精神病学]