NMDA受体介导神经突触可塑性机制与学习记忆高度相关，其表达异常可能是轻度认知功能障碍（MCI）的发病机制。本课题选用自然衰老大鼠加喂半高脂饲料构建老年认知功能障碍大鼠模型，并以临床应用有效的经典化痰古方涤痰汤进行干预，采用Morris水迷宫评价大鼠学习记忆水平，超微电镜观察海马神经元病理改变，免疫组化法检测Aβ含量、Aβ生成分泌酶表达，并分别运用免疫组化学、RT-PCR法和Western blot以及电生理学等方法检测核心指标NMDA受体表达，及大鼠海马神经元突触可塑性的变化，从行为学、病理形态、分子生物学水平观察涤痰汤对轻度认知功能障碍大鼠NMDA受体介导神经突触可塑性机制的影响，有望阐明NMDA受体介导神经突触可塑性与Aβ生成相互影响的作用机制，以及该方的作用及其机理，为中医药防治MCI的深入研究提供实验依据。

N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic plasticity mechanisms are highly related to learning and memory. The abnormal expression of NMDA receptor may be a precursor state of mild cognitive impairment (MCI), Alzheimer's disease (AD) pathogenesis.In this research proposal, natural aging rats fed with a semi-high fat diet will be selected to establish with cognitive dysfunction rat model. Then a traditional Chinese medicinal prescription that with phlegm effect 'Ditan Decoction' (DTD) will be applied on the rat model; learning and memory abilities will be evaluated by using the Morris water maze; pathological changes of hippocampal neurons will be observed under the advanced Micro Devices and electron microscopy; Aβ content and Aβ generated secretion of enzyme expression will be analyzed via Immunohistochemical assay; NMDA receptor expression and rat hippocampal neurons highlights the plasticity changes will be analyzed as a core index of mechanisms, by using Immunohistochemistry, RT-PCR, Western blot, and electrophysiological methods respectively. To sum up, the mild cognitive impairment of NMDA receptor-mediated synaptic plasticity mechanisms on rats mediated by DTD will be evaluated systematically from the behavior, pathology, molecular biology level. Therefore,the outcomes of this presearch proposal can lay the foundation for the further research of AD prevention and new drug exploitation based on DTD.