神经炎症反应是导致脑衰老相关神经退行性疾病的基础病理因素，但其发生机制仍不明确，亦缺乏有效干预措施。NLRP3炎症小体是介导神经炎症反应的关键因子，而TXNIP是介导NLRP3炎症小体激活的枢纽分子；我们前期研究显示，老龄大鼠脑组织中TXNIP表达及NLRP3炎症小体激活均增加，提示TXNIP介导NLRP3炎症小体活化可能是神经炎症反应发生的主要机制。三七总皂苷具有良好的抗炎抗氧化和延缓衰老等药理作用，我们近期结果显示，三七总皂苷可抑制老龄大鼠脑组织中NLRP3炎症小体活化和TXNIP表达，提示其延缓脑衰老机制与抑制神经炎症反应相关。据此，本项目拟采用自然衰老大鼠模型，运用免疫荧光、免疫共沉淀和siRNA等技术，研究TXNIP介导NLRP3炎症小体活化在衰老大鼠神经炎症反应中的作用及三七总皂苷的干预，从而探讨脑衰老神经炎症反应发生的分子机制，并为脑衰老相关神经退行性疾病的防治提供新思路。

Neuroinflammatory response is recognized as an important pathological factor of age-related neurodegenerative diseases. However, its mechanism and effective intervention measures are still distressed. NLRP3 inflammasome plays a key role in mediating the neuroinflammatory response. Recent studies have shown that TXNIP is a pivotal molecule to mediate NLRP3 inflammasome activation. Our previous studies have shown that TXNIP expression and NLRP3 inflammasome activation are increased in brain tissue of aging rats, which indicates that TXNIP mediated NLRP3 inflammasome activation may be the main mechanism of neuroinflammation of aging rats. Total saponins of Panax notoginseng (TPNS) exhibit promising anti-inflammatory, antioxidative and anti-aging activities. Our recent results demonstrate that TPNS inhibit NLRP3 inflammasome activation and TXNIP expression in brain tissue of aging rats, suggesting that the mechanism of retardation brain aging may be related to inhibit neuroinflammation. Therefore, this project will employ natural aging rat model and take siRNA, immunofluorescence and co-immunoprecipitation technologies to study the effects of TXNIP mediated NLRP3 inflammasome activation on the neuroinflammatory response of aging rats, and TPNS modulation, which will provide the new strategy for the treatment of age-related neurodegenerative diseases.