脑卒中后，来源于外周的免疫细胞被招募入脑，加重了受损脑组织的神经炎症反应。前期工作通过流式细胞分选及RNA测序的方法，发现并命名了LncRNA-Maclpil，其高度特异的表达在由外周单核细胞迁移入脑并极化成的巨噬细胞中。由于其靶基因LCP1与免疫细胞的迁移功能密切相关，我们推测降低Maclpil的表达可抑制单核细胞迁移入脑，缓解卒中引起的脑损伤。本课题拟通过体外培养原代单核细胞，利用敲降和过表达系统，从正反两方面探究Maclpil是否可通过抑制其靶基因LCP1的表达，降低外周单核细胞的迁移能力。建立卒中小鼠模型，通过静脉注射Maclpil-siRNA脂质体颗粒的方法，检测在体内敲低Maclpil后，外周单核细胞迁移入脑的数量变化；检测该方法对小鼠脑梗死体积、行为学、生存率等方面的影响。本项目旨在研究影响外周单核细胞迁移能力的分子机制及干预方法，以期为缓解卒中后的神经炎症反应提供新思路。

After ischemic stroke, the peripheral immune cells are recruited into the ischemic hemisphere, exacerbating the neuroinflammation. Our results showed that after ischemia, there are tons of peripheral monocytes derived macrophages in the ischemic hemisphere. Using the flow cell cytometer and RNA sequencing techniques, we showed that these monocytes derived macrophage specifically expressed a LncRNA. The target gene of this LncRNA is LCP1, functioning in the cell migration. Thus, we termed this LncRNA as Macrophage contained LCP1 related pro-inflammatory lncRNA, Maclpil. Based on these data, in the current project, we plan to test whether the cell migration ability will be affected when the expression of Maclpil is down-regulated in the primary monocytes. We will also test the cell migration capability by increasing or decreasing the expression of LCP1 in vitro. To confirm whether inhibiting Maclpil in vivo influences the monocytes migration, we will establish mice MCAO model, and then i.v. inject Maclpil-siRNA or control-siRNA microparticles to compare the number of peripheral monocytes migrating into the ischemic hemisphere. In addition, we will detect the infract size, the mice behavior and survival rate to study the biological function after Maclpil inhibition. This project aims to study the molecular mechanism of peripheral monocyte migration and provides new insights for stroke treatment.