为什么部分老年人群会出现脑老化认知功能障碍，其机制尚不清楚。NADPH氧化酶介导的氧化应激损伤和NLRP1炎症小体介导的炎症反应均与衰老相关疾病有关。我们前期研究显示，老前期大鼠脑内NADPH表达和ROS生成增加；我们预实验，海马神经元培养10d组NLRP1和IL-1β表达明显增加。人参皂苷 Rg1具有抗衰老、抗氧化等作用，我们前期研究显示，Rg1能减少慢性应激小鼠神经元ROS生成，下调NADPH表达。据此我们提出脑老化过程中神经元NADPH上调，激活NLRP1，导致认知功能障碍，Rg1下调神经元NADPH，抑制NLRP1激活，改善认知功能障碍的假说。本课题：①脑老化过程中神经元NADPH和NLRP1的动态变化及与认知功能障碍相关性；②NADPH对NLRP1调节在脑老化中的作用机制；③Rg1对NADPH和NLRP1的调节对认知功能障碍的影响。本课题研究将为防治脑老化认知功能障碍提供新思路。

Why will some of the elderly population be brain aging-related cognitive dysfunction, and its mechanism is still unclear. NADPH oxidase mediated oxidative stress injury and NLRP1 inflammasome mediated inflammation are associated with many aging-related diseases. Our previous studies have shown that the NADPH expression and ROS production increased in pre-old rat brain. Our pre-experiment showed that NLRP1 and IL-1β expression was significantly increased in hippocampal neurons cultured for 10d. Ginsenosides Rg1 has anti-aging, anti-oxidation effect, our preliminary studies showed that Rg1 could reduce NADPH expression and ROS production in chronic stress mice neurons. Accordingly, we propose hypothesis that, in the course of brain aging, NADPH oxidase is upregulated, and the NLRP1 inflammasome is activated in neurons, which induce the cognitive dysfunction. Ginsenosides Rg1 can reduce neuronal NADPH oxidase, inhibit NLRP1 inflammasome activation, and improve the cognitive dysfunction. In the study: ① To study the dynamic changes and the relationship of brain aging cognitive impairment process and NADPH oxidase and NLRP1 inflammasome activation; ② To study the regulation and mechanisms of NADPH oxidase and NLRP1 inflammasome in brain aging cognitive dysfunction; ③ To study the effects and regulation of Ginsenosides Rg1 on NADPH oxidase and NLRP1 inflammasome activation in brain aging cognitive dysfunction. This study will provide new ideas for prevention and treatment of brain aging cognitive dysfunction.