红车轴草异黄酮对认知损害大鼠NF-κB信号通路及突触可塑性的调节作用  

Regulative mechanism of pratensein on NF-κB signaling pathway and synaptic plasticity in cognitive impairment rats

作　　者：卢盛娟 林兴[1] 雷丹青[1] 

机构地区：[1]广西医科大学,广西南宁530021

出　　处：《中国老年学杂志》2016年第10期2318-2321,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(No.81260674);广西自然科学基金资助项目(No.2013GXNSFAA019146)

摘　　要：目的 探讨红车轴草异黄酮对Aβ1~42致大鼠认知功能损害的保护作用。方法 将75只Wistar大鼠随机分为五组,除假手术组外,其余大鼠海马双侧注射Aβ1~42肽建立认知功能损伤模型,治疗组灌胃给予红车轴草异黄酮,连续3 w。采用免疫组织化学法检测各组大鼠海马神经元退行性。TUNEL法测定各组大鼠海马神经细胞的凋亡率;ELISA实验检测各组大鼠海马组织中白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的表达情况;Western印迹法检测海马组织中核因子（NF）-κB信号通路相关蛋白和突触可塑性相关蛋白的表达情况。结果 红车轴草异黄酮能改善Aβ1~42致大鼠的学习记忆障碍。进一步研究表明,红车轴草异黄酮可显著减弱海马神经元退行性,降低Aβ1~42致海马IL-1β和TNF-α的过度表达;减弱星形胶质细胞和小神经胶质细胞的增生,明显抑制海马NF-κB的活化。此外,红车轴草异黄酮还可增加突触可塑性相关蛋白和脑源性营养因子（BDNF）水平。结论 红车轴草异黄酮对Aβ1~42诱导的学习和记忆损伤有明显改善作用,其机制可能与抑制NF-κB活化,减少神经炎症、调节突触可塑性相关蛋白的表达,以及提高BDNF水平有关。Objective To investigate,the protective effect of pratensein against cognitive impairment induced by Aβ1 -42 in rats. Methods Seventy-five rats were randomly divided into five groups. Except the sham control group, all the rats in the other groups were injected bilaterally in the hippocampus with Aβ1-42 peptide to establish the model of cognitive impairment. Then the rats in the treatment groups were administered orally pratensein for 3 weeks. The neuronal degeneration and neuronal apoptosis in hippocampus were detected by immunohistochemistry and TUNEL assays, respectively. The levels of NF-κB and synaptic-associated proteins were examined by Western blot. In addition,the expressions of IL-1β and TNF-α in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. Results Pratensein treatment significantly ameliorated learning and memory deficits induced by Aβ1-42 in rats. The further mechanism study indicated that pratensein significantly reduced the neuronal degeneration and apoptosis in hippoeampus. Moreover, treatment with pratensein significantly decreased the contents of IL-1β and TNF-α, and inhibited the proliferations of astrogliosis and mierogliosis in hippocampus. Pratensein could significantly suppress the activation of NF-κB in hippocampus. In addition, pratensein was able to enhance the levels of synaptophysin and brain-derived neurotrophic factor（BDNF）. Conclusions Pratense can improve the learning and memory deficits induced by Aβ1 -42 in rats, and its mechanism may be relate to the inhibition of neuronal inflammation by suppressing NF-κB activation, and the up-regulations of synapse-related proteins and BDNF level.

关 键 词：红车轴草异黄酮 认知功能损害 核转录因子-ΚB 脑源性营养因子 突触 

分 类 号：R74[医药卫生—神经病学与精神病学]