阿尔茨海默病在临床上尚无有效的治疗方法。我们前期研究发现纳米PEG-PEI介导siROCK2应用AD表现出良好的体外性能，进一步的体内实验发现其可以改善AD模型鼠的学习和记忆能力，然而其作用机制尚不清楚。因此我们提出的科学问题是：PEG-PEI介导siROCK2缓解AD的机制是什么？我们前期体外预实验发现PEG-PEI介导siROCK2可以抑制小胶质细胞的活化，进一步的预实验发现其可下调小胶质细胞的NLRP3，caspase1的表达。因此，依据前期研究成果，我们提出的科学假设是：PEG-PEI介导siROCK2通过调控小胶质细胞自噬抑制NLRP3炎症小体介导的神经炎症缓解AD。本项目拟应用纳米技术将PEG-PEI载体介导siROCK2，处理细胞或植入APP/PS1双转基因模型鼠，通过行为学，免疫荧光，免疫组化及分子生物学等手段验证上述假设，通过多学科交叉创新为AD治疗提供新策略和理论指导。

There is no effective way to prevent the progression of Alzheimer disease till now. Our previous studies have found that PEG-PEI/siROCK2 applying to the treatment of AD showed good performance in vitro. Further in vivo experiments have found that it can improve the learning and memory ability of AD model mice. However, the possible mechanism is unclear. Therefore, we propose the scientific question: what is the mechanism of PEG-PEI mediated siROCK2 alleviating AD? Our preliminary experiments have indicated that PEG-PEI/siROCK2 could inhibit the activation of microglia in vitro. Further studies show that it can down regulate the expression of NLRP3 and caspase1 in microglia. On the basis of our previous research findings, we propose a scientific hypothesis: PEG-PEI/siROCK2 would regulate autophagy in microglia, therefore inhibiting neuroinflammation mediated by NLRP3, which consequently leading to the alleviation of AD. This project aims to use nanotechnology to mediating siROCK2 by PEG-PEI, which implying to treat cells or implant into APP/PS1 double transgenic mouse model, through behavior, immunofluorescence, immunohistochemistry and molecular biology method to verify the above assumptions. We hope to provide new methods and theoretical guidance for AD by the interdisciplinary innovative treatment.