PDF(Pubmed)
Abstract：
Preconditioning with lipopolysaccharide (LPS) induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are resident immune cells of the central nervous system (CNS) that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, - using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins signal transducer and activator of transcription1/2 (STAT1/2).
摘要：
用脂多糖（LPS）预处理诱导针对随后的脑缺血损伤的神经保护，主要涉及先天免疫途径。小胶质细胞是中枢神经系统（CNS）的固有免疫细胞，通过类似记忆的差异重编程对危险信号做出早期反应。然而,预处理的细胞特异性分子机制尚不完全清楚.为了阐明预处理对小胶质细胞的不同分子机制，我们比较了这些细胞特异性的蛋白质组谱响应LPS预处理和没有预处理和随后的短暂局灶性脑缺血和再灌注，-使用建立的短暂性局灶性脑缺血和再灌注的小鼠模型。蛋白质组学工作流程，基于通过细胞分选从小鼠大脑中获得的分离的小胶质细胞，并与质谱联用以进行鉴定和定量，已应用。我们的数据证实LPS预处理诱导显著的神经保护,如脑梗塞体积显着减少所示。建立的脑细胞分离方法适用于获得富集的小胶质细胞级分，以进行有效的蛋白质组学分析。结果表明，LPS预处理对I型干扰素小胶质细胞蛋白质组模式有显著影响，推测由干扰素簇调节蛋白信号转导和转录激活因子1/2（STAT1/2）驱动。
