最新研究发现，2型糖尿病患者有70％的风险发展为痴呆，尤其是女性，雌激素功能紊乱是其发病的重要原因；分析表明，雌性糖尿病模型动物认知障碍的形成机制可能与脑内雌激素受体（ERα）的O-GlcNAc糖基化修饰异常有关。经方当归芍药散（DSS）能改善痴呆病人临床症状及改善糖尿病模型小鼠的认知障碍，其健脾利湿拆方（FBZ）能改善雌性痴呆大鼠模型记忆能力、提高雌激素含量，也能改善高糖损伤细胞中雌激素受体水平。本课题探讨DSS和FBZ治疗雌性糖尿病小鼠认知障碍的机制。采用雌性STZ糖尿病小鼠和自发性糖尿病db/db小鼠模型，以及高糖损伤的HT22和BMECs细胞模型，观察DSS及FBZ对脑内或细胞中ERα的O-GlcNAc糖基化水平，以及神经炎症、氧化应激水平和体内模型认知功能的影响， 探讨DSS尤其是以治痰为重的FBZ防治糖尿病性痴呆的分子药理机制，为研制出能延缓糖尿病性痴呆进程的中药新药提供依据。

Recent studies have found that individuals with type 2 diabetes are at 70% greater risk for the development of dementia compared with those without diabetes, especially in women. The dysfunction of estrogen is an important reason for this disease. Analysis shows that the formation mechanism of cognitive impairment in female diabetic animal model may relate with abnormal O-GlcNAcylation of estrogen receptor (ERα) in the brain. Dangdui-Shaoyao-San (DSS), a classical prescription, was found to improve cognitive dysfunction of patients and diabetic model animals of dementia. In addition, its decomposed recipe, jianpi-lishi recipe (FBZ) could improve cognitive impairment and the concentration of estrogen in female mice with dementia. In high glucose-treated cells, FBZ could also elevate the protein level of ERα. In this study, we employed STZ diabetes and db/db mouse models and high glucose-treated HT22 and BMEC cell models to observe the effect of DSS and FBZ on the O-GlcNAcylation level of ERα. Meanwhile, we will examine the effects of DSS and FBZ on neuroinflammation, oxidative stress and cognitive function to determine functional mechanisms of DSS, especially FBZ, and provide a new way in the treatment of diabetic dementia.