①小胶质细胞激活呈现两种极化表型（M1：神经毒性；M2：神经保护）。卒中后，减少小胶质细胞M1表型，使其向M2转化，对于减轻炎症反应、促进神经再生及功能恢复有重要意义和转化前景。毛柳甙在卒中早期具有保护作用，可能干预小胶质细胞相关炎症反应，但对白质损伤的远期作用及对小胶质细胞极化的影响及机制，尚缺乏研究。②我们前期研究发现：毛柳甙改善脑缺血远期神经功能，经其处理的小胶质细胞吞噬功能加强，促进少突胶质祖细胞分化，提示其可能干预小胶质细胞极化在脑缺血中发挥保护作用。③本项目基于脑缺血模型和原代细胞氧糖剥夺模型，揭示毛柳甙对白质完整性和远期神经功能的保护作用；阐释对小胶质细胞极化的调节作用；研究干预小胶质细胞极化在神经突起、髓鞘再生及炎症中的作用。项目旨在揭示毛柳甙的新作用、新机制，为毛柳甙及M2小胶质细胞治疗缺血性卒中提供新理论支持。

1.Microglia can be polarized into classically activated (M1) and alternatively activated (M2) phenotypes. M1 phenotype produces pro-inflammatory cytokines and toxic metabolites, while M2 phenotype release numerous protective and trophic factors. It is advantageous to reduce the M1 phenotype of microglia and promote the shift to M2 phenotype after stroke. M2 phenotype is helpful in reducing inflammatory reaction, promoting nerve regeneration and improving neurological function. Previous studies revealed that salidroside had a protective effect on the early stage of stroke, which may be involved in alleviation of inflammatory response related to microglia after stroke. However, the long-term effect of salidroside on the white matter injury and its effect and mechanism on microglia polarization after ischemic stroke is still unknown. 2. Our previous study found that salidroside improved the neurological function in cerebral ischemia; after the treatment with salidroside in M1 phenotype, phagocytic function of microglia was strengthened. Moreover, microglia polarization promoted the differentiation of oligodendrocyte precursor cells. These results suggested that salidroside had a protective effect on stroke by regulating microglia polarization. 3. In this project, we use the mice model of cerebral ischemia and the primary cells under oxygen glucose deprivation to verify the following hypotheses: I, salidroside remains the white matter integrity and has a long-term neurological protective effect on cerebral ischemia; II, salidroside regulates microglia polarization; III, salidroside protects neuronal cells, promotes remyelination and inhibits inflammatory response. The aim of this project is to explore the new effect and mechanism of salidroside on cerebral ischemia, and to provide a new theoretical evidence for the treatment of ischemic stroke with salidroside or M2 phenotype microglia.

研究背景：小胶质细胞激活呈现两种极化表型（M1：神经毒性；M2：神经保护）。卒中后，减少小胶质细胞M1表型，使其向M2转化，对于减轻炎症反应、促进神经再生及功能恢复有重要意义和转化前景。毛柳甙在卒中早期具有保护作用，可能干预小胶质细胞相关炎症反应，但对白质损伤的远期作用及对小胶质细胞极化的影响及机制，尚缺乏研究。主要研究内容：1. 探究毛柳甙对缺血性卒中白质完整性和远期神经功能的保护作用。2. 阐释毛柳甙对小胶质细胞极化表型转换的调节作用3. 研究毛柳甙干预小胶质细胞极化对氧糖剥夺神经元损伤的保护作用和少突胶质祖细胞增殖分化的作用。重要结果及关键数据：我们研究发现：在小鼠脑缺血模型中，毛柳甙减少脑缺血梗死体积和脑组织缺失，改善脑缺血后远期运动神经功能和学习记忆功能，增加M2小胶质细胞极化，减少M1小胶质细胞数量，并减轻缺血后白质损伤。毛柳甙可以促进M1小胶质细胞向M2小胶质细胞极化，减少炎症因子分泌，增强吞噬功能，促进原代少突胶质祖细胞分化，减轻氧糖剥夺后原代神经元的损伤。科学意义：本项目基于脑缺血模型和原代细胞氧糖剥夺模型，揭示毛柳甙对白质完整性和远期神经功能的保护作用；阐释对小胶质细胞极化的调节作用；研究干预小胶质细胞极化在神经元损伤、髓鞘再生及炎症的作用。项目揭示了毛柳甙的新作用，为毛柳甙及M2小胶质细胞治疗缺血性卒中提供新理论支持。