【摘要】 目的以Aβ_25-35为工具药,观察小胶质细胞激活后形态和功能的变化,以探讨阿尔茨海默病发病过程中活化的小胶质细胞对神经元损伤作用的可能机制。方法用Aβ_25-35处理体外培养的大鼠小胶质细胞,采用倒置相差显微镜观察细胞形态,RT-PCR方法检测炎性因子肿瘤坏死因子（TNF）-α、白介素（1L）-1β、诱导型一氧化氮合酶（iNOS）mRNA表达,Griess反应检测一氧化氮（NO）生成量,超氧化物岐化酶可抑制的WST-1还原法检测细胞外超氧化物产生量。结果Aβ_25-35作用后,小胶质细胞形态发生明显变化,细胞胞体延长。由胞体伸出一个或多个树枝状突起,变为类巨噬样细胞;细胞外超氧化物产生量明显增加;但TNF-α、IL-1β、iNOSmRNA表达及NO释放量无明显改变。结论Aβ_25-35激活小胶质细胞以活性氧类物质产生为主,活性氧类物质在介导Aβ诱导的神经毒性中起了关键作用。更多还原

【Abstract】 Objective To investigate the possible inflammatory mechanisms of Alzheimer’s disease by observing the morphological and functional changes of cultured microglias activated with the tool drug of Aβ_25-35.Methods In vitro cultured rat microglias stimulated with Aα_25-35,the inverted phase contrast microscope was applied to observe the morphological changes of microglias; RT-PCR assay was applied to detect mRNA expression levels of the inflammatory factors of TNF-α,IL-1βand iNOS;Griess reaction was applied to measure NO release;and SOD-inhibitable reduction of WST-1 assay was applied to determine the production of extracellular superoxides.Results After being activated with Aβ_25-35,the microglia showed an obvious morphological change,the cell soma becoming extended and one or more dendritic structures protruding from the cell somas,to become macrophage-like cells;the production of extracellular superoxides increased evidently.However,Aβ_25-35 activation had no significant effect on mRNA expressions of TNF-α,IL-1βand iNOS,and NO release. Conclusion Aβ_25-35-activated microglias mainly produce reactive oxygen species,which play a key role in mediating Ale-induced neurotoxicity.更多还原