固本健脑法对Alzheimer病细胞模型Sorla阻断APP裂解通路机制的调节作用研究

Alzheimer's Disease is a refractory disease and is still lack of efficiency drug to treat it. Chinese medicine is an advanced remedy method with its convenience, high efficiency and less side effects. Our previous research work suggested that Guben-Jiannao remedy is beneficial for treating AD, via regulating Caveolin-1, which increases the cognition of AD. But how the drugs regulate the pathway is unknown. It has been reported that the level of SorLA is co-related with the activation of APP pathway in AD. These indicated that SorLA inhibiting APP pathway plays an important role in the mechanism of AD, and we therefore hypothesize that Guben-Jiannao exerts its anti-AD effect via the pathway. In this application, we propose to investigate the relationship between Guben-Jiannao and SorLA inhibiting APP pathway in a cell model of AD by measuring SorLA、BACE1、PS-1、APP mRNA and protein expression. The results will provide further support for the clinic practice of the Guben-Jiannao and will open up new research strategies and methods for studying AD.

老年性痴呆（AD）是一种难治性疾病，目前尚缺乏特别有效的治疗药物。探求新的治疗靶点及策略已成为现代医学研究的热点与难点。前国家自然基金项目研究发现，固本健脑方能显著改善AD 模型大鼠学习记忆能力。最新研究揭示，SorLA可通过APP、PS-1、BACE-1等因子形成APP裂解通路，调控Aβ的生成与聚集。提示SorLA在AD的发病中具有重要作用，固本健脑方的机制可能与此有关。本研究将在前期研究基础上，围绕APP裂解通路开展研究，通过免疫荧光和免疫共沉淀法，评价/证实SorLA与BACE1、PS-1、APP在细胞中的共定位及相互作用，结合Real-Time PCR和Western Blot相互映证固本健脑法干预前后SorLA、BACE1、PS-1、APP的表达变化，观察固本健脑法对APP裂解及Aβ生成、沉积的影响。实验结果将为中医药治疗老年痴呆研究提供新的策略和方法.

老年性痴呆（AD）是一种难治性疾病，目前尚缺乏特别有效的治疗药物。探求新的治疗靶点及策略已成为现代医学研究的热点与难点。前国家自然基金项目研究发现，固本健脑方能显著改善AD 模型大鼠学习记忆能力。最新研究揭示，SorLA可通过APP、PS-1、BACE-1等因子形成APP裂解通路，调控Aβ的生成与聚集。提示SorLA在AD的发病中具有重要作用，固本健脑方的机制可能与此有关。本研究在前期研究基础上，构建稳定转染人APPsw基因的SH-SY5Y细胞（APPsw细胞）为模型细胞，以转空质粒的neo细胞作为对照，围绕APP裂解通路开展研究，通过免疫共沉淀法，结合Real-Time PCR和Western Blot相互映证评价并证实了SorLA与BACE1、PS-1、APP在细胞中的共定位及相互作用.发现固本健脑法能够显著提高模型细胞SorLA的表达，促进APP裂解，从而抑制Aβ生成、沉积，起到改善AD病理改变的作用。实验结果证实固本健脑法是治疗AD的有效治法，其机制可能与调控细胞内SorLA表达有关。本研究为中医药治疗老年性痴呆提供了新的靶点和方法。