固本健脑液对AD模型的作用及Caveolin-1、P-tau影响的研究

Alzheimer's disease (AD) is one of the most important social, healthy and economic crisis of the 21st century. Traditional Chinese Medicine , especially the local characteristics of drug is attracted widespread attention,for the efficacy treatment of AD and itsnatural advantage. Chinese medicine believes that "the old are spleen and kidney deficiency , phlegm block " is the basic mechanism of AD .This project intends on the basis of preliminary studies , around the caveolin- 1 protein is a key role in learning and memory , and tau protein hyperphosphorylation injury may be the AD onset and core mechanism , using of advanced technologies and methods of transfection and gene silencing to observe the Guben Jiannao Liquor regulating Caveolin-1 protein levels, inhibition of the hyperphosphorylation of tau protein to protect the signaling function of dendritic spines , the role of depth from the molecular level systems in order to strengthen our foundation and mechanism of the prevention and treatment of AD and improve action learning and memory abilities by Guben Jiannao Liquor .

阿尔茨海默病（AD）是21世纪最重要的社会、健康及经济危机之一。中医药尤其是地方特色药物治疗AD以确有疗效及药自天然的优势，而受到广泛关注。中医认为年老"先后天之本亏虚，痰瘀阻滞"是AD的基本病机。本课题拟在前期研究基础上，围绕Caveolin-1蛋白在学习记忆中的关键作用及tau蛋白过度磷酸化损伤可能是AD肇始和核心机制，采用质粒转染及基因沉默等先进技术和方法，观察固本健脑液调节Caveolin-1蛋白水平、抑制过度磷酸化的tau蛋白、保护树突棘的信号传导功能等作用，以期从分子水平系统深入探讨固本健脑液预防和治疗AD并改善其学习记忆能力的作用机制。

本研究在前期研究基础上，对具有地方特色的防治老年痴呆药物“固本健脑液”对AD的作用及相关机制进行了研究。首先以SD大鼠海马注射Aβ1-42复制AD动物模型，予固本健脑液灌胃，以盐酸多奈哌齐为对照，通过水迷宫试验观察临床疗效；并通过对海马石蜡切片、高尔基染色观察神经元突触的改变；Western blot法、RT-PCR检测大鼠海马中Caveolin-1蛋白、P-tau蛋白（Thr231，Ser396）等含量的变化。然后培养胎鼠原代海马神经元，运用质粒转染及基因沉默技术制备AD细胞模型；普通SD大鼠灌胃，提取空白血清和含药血清，并作用于AD细胞模型，Western blot定量分析P-tau(Thr231，Ser396)\caveolin-1的水平等指标。结果表明，固本健脑液对AD动物模型学习记忆能力有明显改善，并可增加AD模型海马神经元及突触数量，其机制可能与提高Caveolin-1蛋白水平，抑制tau蛋白过度磷酸化等有关。