小胶质细胞（MG）作为中枢的免疫细胞，具有清除Aβ的作用，然而过度活化的MG在促进炎症因子释放的同时，也降低了对Aβ的吞噬能力。MG功能的双面性与其活化后的表型有关，因而调控MG的活化表型，使其趋利避害将是抗AD药物研究的新方向。髓样细胞触发受体（TREM）可抑制MG过度活化、增强其吞噬能力。研究显示TREM2的变异与AD的发生密切相关。因此，TREM2有可能是调控MG表型转变的关键。前期研究显示，红花黄色素（SY）可明显改善痴呆动物的学习记忆能力，减少脑组织Aβ沉积，抑制MG过度活化。本课题以TREM2为研究靶点，采用siRNA干扰技术下调APP/PS1转基因小鼠脑组织和BV-2小胶质细胞中TREM2的表达，观察其在调控MG活化表型、改善Aβ病理变化中的作用，同时观察SY是否通过调控TREM2的表达，抑制MG过度活化发挥抗AD作用，希望能寻找一种可延缓AD发病进程的药物。

Microglia (MG), as an immune cell in the central nervous system, which has been found have the effect to clear Aβ. However, the over-activated MG can promote the release of inflammatory cytokines and reduce its phagocytosis for Aβ. Depending on the activated phenotypes, microglia can produce two-sided of functions. Therefore, regulating the specific switching of MG phenotypes to foster strengths and circumvent weaknesses, may provide new direction for the drug research of AD. Triggering receptor expressed on myeloid cells (TREM) can inhibit the over-activation of MG, and enhance its phagocytosis. Studies found that the variation of TREM2 is closely related to the occurrence of AD. Therefore, TREM2 is crucial to the shift of MG phenotypes. Previous studies showed that safflower yellow (SY) can significantly improve the learning and memory ability of dementia animals, reduce Aβ deposition in brain, and inhibit the over-activation of MG. In this study, we will take TREM2 as research target. Using siRNA interference technique to down-regulated the expression of TREM2 in APP/PS1 transgenic mice and BV-2 microglial cell. We will observe the effect of TREM2 on regulating MG phenotypes and improving the Abeta pathological changes. Meanwhile, we will also investigate whether SY exert the therapeutical effect for AD by regulating the expression of TREM2 and inhibiting the over-activated of MG.The project is expected to find a drug to delay the progress of AD.