基质细胞衍生因子1对阿尔茨海默病小鼠脑内Aβ的清除作用

Stromal cell-derived factor 1 decreases β-amyloid deposition in Alzheimer＇s disease mouse model

目的 观察基质细胞衍生因子1（SDF-1）对阿尔茨海默病小鼠脑内β淀粉样蛋白（Aβ）的清除作用,并研究其作用机制.方法 将12只APP/PS转基因小鼠按随机数字表法分为治疗组和对照组,治疗组给予侧脑室SDF-1注射,对照组给予侧脑室磷酸缓冲盐溶液（PBS）注射,每周1次,连续注射8周.治疗8周后,采用免疫荧光组织化学方法观察并比较2组注射后小鼠脑内Aβ斑块的数量和面积,以及小胶质细胞分布及斑块相关的小胶质细胞的数量.结果 治疗8周后,治疗组小鼠海马区域Aβ斑块的相对面积和数量为（0.4527±0.0711）％和（0.004 837±0.001 074）％,与对照组比较,差异均有统计学意义（P＜0.05）;治疗组小鼠皮质区域Aβ斑块的相对面积和数量与对照组比较,差异亦均有统计学意义（P＜0.05）.治疗8周后,治疗组海马和皮质区域斑块相关的小胶质细胞的数量与对照组比较,差异均有统计学意义（P＜0.05）.结论 SDF-1α侧脑室注射可能减少APP/PS1小鼠脑内Aβ的斑块,其作用机制可能是SDF-1增加了小胶质细胞向Aβ斑块的趋化作用,从而促进Aβ斑块的吞噬清除.

Objective To explore whether stromal cell-derived factor 1 （SDF-1） can promote the clearance of β-amyloid deposition in the brain of APP/PS1 mice and the possible underlying mechanism.Methods Twelve 28-week-old APP/PS1 mice were divided into two groups：a treatment group and a control group.Animals were given the intracerebroventricular injection weekly with PBS or mouse recombinant SDF-1 α for eight weeks.Microglia and Aβ in cerebral cortex and hippocampal region of APP/PS1 mice were detected by immunofluorescence.Results After 8-week treatment,both the relative number and the relative area of Aβ deposits in the mice of treatment group were less than those in the control group.The relative number of plaque associated microglia increased to a significantly greater extent in the cortex and hippocampus in treatment group than those in the control group.Conclusion Injecting SDF-1α significantly reduced amyloid burden in APP/PS1 mice.This effect might associated with the improvement of the chemotoxis of microglia,which promote the phagocytosis of Aβ by microglia.