基于Aβ产生和突触功能调节研究开心散加味新方治疗阿尔兹海默病的作用机制

经典名方开心散具有明确的治疗老年痴呆症（阿尔兹海默病，AD）作用，临床和实验研究表明，AD存在明显的血瘀病理特征，但开心散原方活血祛瘀之力偏弱。我们前期选择具有活血祛瘀功效且具有抗AD活性的中药加入开心散组成开心散加味新方，研究表明开心散加味后抗AD作用增强，且能促进开心散原方抗AD活性成分在脑内的分布，提高原方的生物利用度。本项目拟采用携带多基因突变位点的AD小鼠模型，并采用体外培养的AD病理细胞模型，进一步对比研究上述两方的抗AD作用，并基于Aβ级联假说，进一步选择Aβ产生的始动环节与最直接反映AD认知功能改变的突触结构和功能调节的较终末环节两个关键节点，同时结合活体分子及功能影像学技术，较系统地研究上述两方治疗AD的不同作用特点和机理，从而从上述角度阐明开心散活血化瘀加味治疗AD的配伍内涵，为临床AD的中医药治疗和进一步中药新药研发提供现代生物医学依据和前期实验研究基础。

Kai-Xin-San, a famous classical prescription in traditional Chinsese medicine (TCM), has been proved with clear effects in treating Alzheimer's disease (AD). Among the pathological characteristics of AD, the blood stasis is obviously one aspect of the pathological features of this disease, but Kai-Xin-San is lack of efficacy in promoting blood circulation and removing blood stasis. Previously, a new prescription, the Modified Kai-Xin-San, was set up by us by adding several traditional Chinese herbs to Kai-Xin-San, these added Chinese herbs were identified with the efficacy in removing blood stasis and with the activity in treating AD. Our previous results showed that, compared with Kai-Xin-San, the novel Modified Kai-Xin-San showed more efficacy in treating AD, the content levels of the active ingredients with the anti-AD activity in Kai-Xin-San were also found increased in the brains of the Modified Kai-Xin-San-treated animals, which indicates that, the modified new prescription could improve the bioavailability of the original prescription. In this project, according to the amyloid cascade hypothesis in AD pathology, an AD mouse model which carrying multiple mutation genes in AD patients and two kinds of in vitro cultured cells with the pathological characteristics of the AD were used to study the effects of Kai-Xin-San and the Modified Kai-Xin-San in treating AD. Besides these, their underlying mechanisms based on the modulation of the Aβ production and the regulation of the synaptic function will also be investigated in this project. In addition, the in vivo molecular and functional imaging technologies will also be applied in this project in order to further clarify the characteristics of the effects of these prescriptions in treating AD. These above researches may provide us useful references and the experimental basis for AD treatment in TCM clinic and for further research and development of new TCM drugs.