阿尔茨海默病患者脑内有大量被激活的小胶质细胞，产生大量炎症介质，毒害神经元，影响认知功能。因此，调控小胶质细胞的活性，使其向保护神经元的方向发展是研究之关键。前期研究发现，肉豆蔻木酚素（Macelignan）可抑制小胶质细胞的过度激活及pERK和mTOR的异常表达，显著改善AD模型大鼠认知功能障碍，显示其良好的抗炎和神经保护作用。近年来，小胶质细胞对神经元的调节作用渐被关注，但PI3K介导mTOR和FoxO3a信号通路调控小胶质细胞极化表型，改善AD认知功能的机制及肉豆蔻木酚素的干预作用尚未见报道。因此，本研究拟利用神经炎症和慢性血管性痴呆模型大鼠，研究在AD中PI3K介导mTOR和FoxO3a信号通路对认知功能的作用，探讨肉豆蔻木酚素对AD脑损伤的影响，明确小胶质细胞对神经元及AD大鼠认知功能的调控机制，阐明肉豆蔻木酚素的作用靶点，研究成果将为抗AD天然药物的开发及其防治提供科学依据。

Microglia activation produced inflammatory mediators to damage neurons in AD, and as a result, cognitive function is badly affected. Therefore, the key of study is to regulate microglial function and make its development direction turn to protect the neurons. Our previous study showed that the transition Nutmeg guaiacol prime (Macelignan) could inhibit the excessive activation of microglia and the abnormal expressions of pERK and mTOR, and improved the cognitive function in AD model rats. The results indicated that macelignan played anti-inflammatory and neuroprotective roles in AD rats. In recent years, the role of microglia regulation neurons function has been gradually concern, however, the mechanism of PI3K/mTOR and FoxO3a signaling pathways regulation microglia polarized phenotype to improve the cognitive function and intervention role of macelignan in AD rats has not been reported. In this study, we will investigate PI3K/mTOR and FoxO3a initiate some signaling cascades to regulate cognitive function, and explore the effects of macelignan on the brain injury in AD rats. Finally, we will determine signal transduction in microglia and neurons and the regulation mechanism of cognitive function in AD rats, and clarify the target of macelignan. Our results will provide scientific basis for natural drug development and AD prevention and treatment.