补肾方对阿尔茨海默病CD33-TREM2-NF-κB信号通路的免疫调控及神经保护作用

阿尔茨海默病（AD）是威胁老年人健康的重要疾病，目前仍缺乏明确发病机制和有效治疗。小胶质细胞异常炎性激活是AD突触损害的关键因素之一，髓系细胞分化抗原（CD33）和髓系细胞触发受体-2（TREM2）均为与AD风险相关的小胶质细胞受体，且CD33可能作为TREM2的上游靶点，共同参与调控小胶质细胞的表型转化，调节炎症反应及对Aβ的吞噬，从而发挥神经保护作用。NF-κB是炎症反应下游经典转录因子，因此推测CD33/TREM2受体可能通过激活NF-κB参与AD的病理过程。肾虚作为AD的核心病机，本团队前期临床研究证实补肾方可改善患者认知功能。项目拟通过APP/PS1小鼠探索补肾方调控炎症反应的作用，并运用Transwell共培养SH-SY5Y和BV2细胞进一步验证补肾方通过CD33-TREM2-NF-κB信号途径减轻免疫炎症来介导对阿尔茨海默病的神经保护作用。

Alzheimer's disease (AD) is currently an important disease that threatens the health of the elderly. Studies have shown that myeloid cell differentiation antigen (CD33) and myeloid trigger receptor-2 (TREM2) are microglial receptors related to the risk of (AD) in Alzheimer's disease, and CD33 may be the upstream target of TREM2, play a neuroprotective role by regulating the phenotypic transformation of microglia, regulating inflammatory response and phagocytosis of A β. NF- κ B is a classical transcription factor downstream of inflammatory response, so it is speculated that CD33/TREM2 receptor may participate in the pathological process of AD by activating NF- κ B. Kidney deficiency is the core pathogenesis of AD. Our team's previous clinical studies have confirmed that tonifying kidney can improve the cognitive function of patients. This project intends to explore the inflammatory response and its mechanism of Kidney-tonifying formula through APP/PS1 mice, and use Transwell co-cultured SH-SY5Y and BV2 cells to further verify that the kidney tonifying prescription can reduce immune inflammation through CD33-TREM2-NF- κB signal pathway and mediate the neuroprotective effect in Alzheimer's disease.