Fractalkine通过靶向调节小胶质细胞CD163/SHH表达促进脑出血后血肿吸收和神经血管修复的研究

血肿的主要成分红细胞及其降解产物是引发脑出血后继发损害的关键因素，其主要由血红蛋白清除受体CD163介导M2型小胶质细胞清除，但这个病理过程存在M2型小胶质细胞在血肿周围出现时间较迟和神经元的CD163同时介导神经元损伤的问题。我们前期在小鼠脑出血模型高通量筛选和小规模临床观察等发现神经元表达的Fractalkine与脑血肿的吸收相关，其可通过唯一受体CX3CR1特异性的作用于M2型小胶质细胞，并靶向促进M2型小胶质细胞表达CD163和神经血管修复的关键分子SHH，但其具体的分子机制仍有待进一步研究。本研究拟在采用基因敲除小鼠、免疫荧光共聚焦、磁共振显像等多种方法，探讨脑出血后 Fractalkine-CX3CR1信号时空变化规律，进一步研究其通过CD163/SHH靶向促进M2型小胶质细胞血肿的吸收和神经血管修复的作用及其分子机制。从而为脑出血的治疗提供新的潜在的治疗靶点。

The main components of hematoma, red blood cells and their degradation products, are the key factors that cause secondary damage after cerebral hemorrhage. They are mainly cleared by M2 microglia through the hemoglobin scavenger receptor CD163. In this pathological process, but M2 microglia appear late around the hematoma and CD163 leads to neuronal damage. We have previously found that Fractalkine is related to the absorption of cerebral hematoma by high-throughput screening in mouse models and small-scale clinical observation. Fractalkine could facilitate migration of M2 microglia to injured neuron by its unique receptor, CX3CR1, promote hematoma absorption and neurovascular repair by CD163 and SHH, but the underlying molecular mechanism remains to be further studied. This study intends to use gene knockout mice, immunofluorescence confocal imaging, magnetic resonance imaging and other methods to explore the spatiotemporal changes of Fractalkine-CX3CR1-CD163/SHH signals after intracerebral hemorrhage, and to further study their effect on hematoma absorption and neurovascular repair and the underlying molecular mechanism. Thus providing a novel potential therapeutic target for the treatment of intracerebral hemorrhage.