阿尔茨海默病（AD）中医病机为本虚标实，本虚为脑髓亏损和气血不足，标实为痰浊血瘀。其病理产物β淀粉样蛋白（Aβ）沉积导致内质网应激，造成脑微血管内皮细胞损伤，介导Aβ转运的LRP-1表达下降及RAGE表达上升，导致Aβ转运、清除异常。SIRT6具有保护AD和调控内质网应激的作用。临床至今尚无通过改善脑微血管内皮细胞功能保护AD的方法。桃红四物汤为中医传统活血化瘀经典方剂，具有较强的血管药理活性。研究表明，桃红四物汤具有神经保护作用，可以缓解血管性痴呆。本课题前期研究发现，桃红四物汤有效改善东莨菪碱诱导的小鼠学习记忆能力障碍，但其分子机制不明。为此，本课题拟从桃红四物汤调节AD动物模型脑微血管内皮细胞功能角度，构建APP/PS1转基因小鼠和Aβ1-42损伤的脑微血管内皮细胞模型，深入探讨SIRT6介导的蛋白乙酰化修饰，缓解脑微血管内皮细胞的内质网应激的分子机制，以减少Aβ，改善AD。

The pathogenesis of Alzheimer’s disease (AD) in Chinese medicine is deficiency in origin and excess in superficiality. "Deficiency in origin" means brain essence deficiency and insufficiency of Qi-Blood. "Excess in superficiality" means phlegm retention and blood stasis. The accumulation of Aβ, the pathological marker of Alzheimer’s disease (AD), can induce the dysfunction of brain microvascular endothelial cells (BMEC) through endoplasmic reticulum stress (ER stress). The reduction of LRP-1 expression and overexpression of RAGE in BMEC result in Aβ accumulation. Sirtuin6 (SIRT6) can protect against AD and downregulate ER stress. Clinically there are still no effective drugs targeting BMEC to clear Aβ from the brain. Taohong Siwu decoction, a famous formula in the traditional Chinese medicine with strong vascular pharmacological effect, can promote blood circulation to remove blood stasis. Taohong Siwu decoction can protect against neural damage in vascular dementia. Our preceding research found that Taohong Siwu decoction could protect against scopolamine-induced memory impairment. However, the mechanism is still unknown. In this study, we aim to investigate the effects of Taohong Siwu decoction on Aβ transport and clearance via SIRT6/ER stress pathway in the BMEC of AD models. APP/PS1 transgenic mice and Aβ1-42-treated BMEC models were employed to provide some evidences of Taohong Siwu decoction in treatment of AD.