【摘要】 目的　探讨 β 淀粉样蛋白 (Aβ)对S10 0 β表达的影响及作用机制。 方法　采用Aβ2 5-3 5和IL 1ra ,选择大鼠海马CA1区进行定位注射 ,通过行为学测试、刚果红染色和免疫组化技术结合图像分析的方法 ,对不同时间大鼠的学习记忆、淀粉样沉积、GFAP和海马CA1区S10 0 β表达的变化进行观测。 结果　Aβ2 5-3 5注射后 ,大鼠的学习记忆能力明显下降 ;海马CA1区出现Aβ沉积 ,并有大量GFAP阳性胶质细胞包绕 ;实验组S10 0 β阳性细胞数目在 3、7、2 1d较对照组均有明显增多 ,细胞平均面积只在 2 1d才有明显增大。脑内注射IL 1ra后 3、7d,S10 0 β阳性细胞数目明显低于同组的Aβ大鼠 ,而高于对照组。结论　Aβ2 5-3 5脑内注射可建立具有类似阿尔茨海默病的局部病理改变和学习记忆损害的AD动物模型 ;Aβ2 5-3 5可上调大鼠海马CA1区S10 0 β的表达 ,实验早期以S10 0 β阳性细胞的数目增加为主 ,后期表现为细胞体积的增大 ;IL 1ra脑内注射可明显降低Aβ2 5-3 5上调S10 0 β表达的作用 ,其机制是阻断由Aβ2 5-3 5激活的小胶质细胞释放的IL 1对星形胶质细胞的活化作用。更多还原

【Abstract】 Objective To explore the mechanism and effects of β-amyloid protein (Aβ) on S100β expression. Method Different intervals after bilateral stereotaxis injection of Aβ 25-35 and interleukin-1 receptor antagonist (IL-1ra) into the CA1 region of the rat hippocampus, learning and memory, amyloid deposition, and the S100β expression in hippocampal CA1 region were analyzed by means of behavior test, Congo red staining, and immunohistochemisty combined with stereologic analysis. Results Twenty-one days after Aβ injection, the learning and memory abilities of the rats were significantly decreased. The amyloid deposition was detected in the hippocampus, the glial fibrillary acidic protein (GFAP) positive astrocytes were found surrounding amyloid deposition. The number of S100β positive cells in experiment group was significantly increased at all time points. The average area of S100β positive cells was increased significantly only 21 days after Aβ injection. The number of S100β positive cells was significantly decreased at 3 and 7 days after IL-1ra injection, and still increased compared with that of control group at each time point. Conclusion Intrahippocampal injection of Aβ 25-35 can cause similar pathologic changes of Alzheimer’s disease (AD), and decrease the learning and memory abilities of rats. Our experiment might provide a useful animal model for study of AD. Aβ 25-35 is capable of up-regulating S100β expression. Cell number increases at the earlier stage of experiment, and cell area increases significantly at end stage. The injection of IL-1ra can attenuate effect of Aβ on S100β expression by blocking the effects of IL-1, which is released from activated microglia induced by Aβ, on activating astrocytes.更多还原