基质细胞衍生因子-1对阿尔茨海默病脑内可溶性Aβ清除作用的研究  

The effect of stromal cell-derived factor 1 on soluble β-amyloid in Alzheimer's disease mouse model

作　　者：汪琦[1,2] 徐逸[1] 王伟[1] 潘邓记[1] 朱舟[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]北京煤炭总医院神经内科

出　　处：《卒中与神经疾病》2015年第3期131-134,共4页Stroke and Nervous Diseases

基　　金：国家自然科学基金项目(NO.81100086)

摘　　要：目的通过对APP/PS1双转基因小鼠侧脑室持续注射基质细胞衍生因子-1(SDF-1),以观察SDF-1对脑内可溶性β淀粉样蛋白(Aβ)的影响及其可能的机制。方法将28周龄的野生型(wild type,WT)小鼠和APP/PS1转基因小鼠分为对照组和SDF-1α干预组,分别予以侧脑室注射SDF-1α和PBS,1周1次,连续注射4周和8周。采用ELISA法检测小鼠脑内可溶性Aβ的水平,采用Wsetern blot方法检测小鼠脑内小胶质细胞标志物Iba-1的水平。结果 SDF-1α侧脑室注射后APP/PS1小鼠脑内可溶性Aβ-40和Aβ-42水平与对照组相比明显减少,APP/PS1小鼠及WT小鼠脑内Iba-1水平较对照组增加。结论 SDF-1α侧脑室注射可能减少APP/PS1小鼠脑内可溶性Aβ的水平,其作用的机制可能是SDF-1α增加了脑内小胶质细胞由外周向中枢的募集,从而促进Aβ的吞噬清除。动员与趋化骨髓来源的小胶质细胞可能成为治疗AD的新靶点。Objective To explore whether treatment with SDF-1α （stromal cell-derived factor 1 ,SDF-1） can regulate the chemotoxis of microglia and decrease soluble 13-amyloid（Al3）. Methods 28-week-old APP/PSI mice and their wild-type littermates were divided into four groups： WT ＋ PBS, WT ＋ SDF-1α, APP/PS1 ＋ PBS and APP/PS1 ＋ SDF-1α. Animals were given the intracerebroventricular injection weekly with PBS or mouse recombinant SDF-1α for 4 weeks or 8 weeks. Brain levels of soluble Aβ40 and Aβ42 were analyzed via ELISA. Iba-1 and microglia marker in APP/PS1 transgenic mice and WT mice were detected by western blot. Results Administration of SDF-1α reduced soluble Aβ40 and Aβ42 levels significantly compared to the control group. Quantification by densitometry of Western blot revealed a significant increase in Iba-1 levels after 4 or 8 weeks of SDF-1α injections in APP/PS1 transgenic mice and WT mice. Conclusions Intracerebroventricular in- jecting of SDF-1α signi cantly reduced amyloid levels in APPS/PS1 mice. This effect maybe associated with the regulation of the chemotoxis for mieroglia from peripheral to central. It is conceivable to propose that bone marrow derived microglia mobilization may be a promising therapeutic target for AD treatment.

关 键 词：阿尔茨海默病 Β淀粉样蛋白 小胶质细胞 基质细胞衍生因子-1 趋化作用 

分 类 号：R749.1[医药卫生—神经病学与精神病学]