大鼠海马内注射β淀粉样蛋白诱导外周血T细胞MIP-1α过表达及其穿过血脑屏障  

High Expression of MIP-1α in Peripheral Blood T Cells by Hippocampus Injection of β-Amyloid Peptide(1～42) Triggers T Cells Entry Into Rat Brain

作　　者：郭大文[1] 马怡然[1] 方文刚[1] 陈誉华[1] 

机构地区：[1]中国医科大学基础医学院发育生物学教研室卫生部细胞生物学重点实验室,沈阳110001

出　　处：《生物化学与生物物理进展》2006年第12期1177-1182,共6页Progress In Biochemistry and Biophysics

基　　金：教育部跨世纪人才基金(2002教技函48号);教育部博士点基金(20040159002);辽宁省科技厅资助项目~~

摘　　要：为观察脑内β淀粉样蛋白(amyloidbeta,Aβ)沉积对外周血T细胞穿过血脑屏障的影响,通过立体定位仪将Aβ1～42肽注射到大鼠双侧海马(以Aβ42～1反序列肽为对照),实时定量PCR(RT-qPCR)检测发现,Aβ1～42上调了外周血T细胞中巨嗜细胞炎症蛋白(macrophageinflammatoryprotein-1α,MIP-1α)的表达,同时免疫荧光分析显示,脑内的Aβ1～42也引起了脑微血管内皮上MIP-1α受体(CCR5)的表达增加,以及伴随的脑实质内T细胞数量的增加.然而,大鼠腹腔内注射抗MIP-1α中和抗体则阻断了Aβ1～42所致的脑内T细胞数量的增加.提示脑内Aβ沉积能诱导外周血T细胞MIP-1α依赖性迁移入脑.In order to investigate the effects of β-amyloid （Aβ） deposits on migration of peripheral blood T cells across blood-brain barrier, Aβ1-42 was stereotaxicly injected into rat hippocampus with reverse peptide Aβ42-1 as control. After 7 days post-injection, the expression of macrophage inflammatory protein-let （MIP-1α） and its receptor （CCR5） in peripheral blood T cells was detected by real-time quantitative polymerase chain reaction （RT-qPCR）. Brain sections were analyzed with immunofluorescence of CD3, VWF and CCR5. The results showed that Aβ1-42 deposits in rat brains led to significantly higher expression of MIP-1α in circulating T cells than Aβ42-1 did, while no increase of CCR5 expression was observed in circulating T cells of Aβ1-42-injected rats compared to Aβ42-1-injected rats. Furthermore, the expression of CCR5 was up-regulated by Aβ1-42 on rat brain microvascular endothelial cells （RBMEC）. In addition, T cells were increased in abundance in Aβ1-42-injected brains compared with Aβ42-1-injected brains, scattered mainly in cortex and hippocampus. Treatment of Aβ1-42-injected rats with neutralizing antibody specific for MIP-1α dramatically blocked the enhanced T cells entry into rat brain. The results implied that the interaction between MIP-1α over-expressed in T cells and CCR5 on RBMECs may contribute to the Aβ1-42-induced circulating T cells migrating across blood-brain barrier.

关 键 词：阿尔茨海默病 β淀粉样蛋白 MIP-1Α T细胞 血脑屏障 

分 类 号：R741[医药卫生—神经病学与精神病学]