大鼠海马内注射β淀粉样蛋白对脑内小胶质细胞活化和神经元凋亡的影响

Beta-amyioid peptide-induced microglia activation and neuron apoptosis in vivo

目的 观察脑内β淀粉样蛋白（β-amyloid，Aβ）沉积早期对脑内胶质活化和细胞凋亡的影响。方法 通过立体定位技术将Aβ1-42注射至大鼠双侧海马，对照组注射反序列Aβ42-1或PBS。分别于注射后3、7、14d，用免疫组织化学和免疫荧光法检测CD11b、MHCⅡ及活化caspase-3的表达。结果 海马内注射Aβ1-42后3d，大鼠脑内CD11b和MHCⅡ阳性小胶质细胞数量[分别为（345．22±75．86）和（200．22±42．88）]，较PBS组[分别为（98．61±20．79）和（35．43±12．46）]和Aβ42-1组[分别为（103．44±22．13）和（43．41±15．63）3明显升高（P〈0．01），7d达到高峰[分别为（486．22±81．51）和（223．62±66．99）]，表现为明显的激活状态。注射后3d，大脑皮质、海马的活化caspase-3阳性细胞数量（132．42±31．80）比PBS组（4．41±3．13）和AB㈨组（4．85±3．70）明显升高（P〈0．01），7d后更明显（165．24±33．95），以海马更为显著。结论 海马内注射A？可以诱导小胶质活化和神经细胞凋亡，有可能作为研究阿尔茨海默病（Alzheimer’s disease，AD）发病早期的动物模型。

Objective To investigate the effect of earlier β-amyloid（Aβ） deposits on microglia activation and neuron apoptosis. Methods The aggregated Aβ1-42 was injected into the hippocampus of rats and the reverse peptide Aβ42-1 or phosphate buffer saline （PBS） was injected as controls. Brain sections were analyzed by immunohistochemistry to determine the expressions of CD11b, MHC Ⅱ and the activated caspase-3. Results The numbers of microglia / MHC Ⅱ positive microglia in the Aβ42-1 group[（103. 44±22.13） and （43.41±15. 63）, respectively] were significant higher than in the PBS group[（98. 61 ± 20.79） and （35.43 ± 12.46）, respectively], and markedly increased at 3 days[（345. 22±75. 86） and （200.22±42.88）, respectively, all P〈0. 01]and reached the top levels at 7 days [（486.22 ± 81.51） and （223.62 ± 66.99）, respectively]. The activated caspase-3 positive cells were more in cortex and hippocampus after Aβ1-42 injection at 3 days （132.42±31.80） and markedly increased at 7 days （165. 24± 33.95）and more evident in hippocampus, than in PBS group （4. 41±3. 13） or Aβ42-1 group（4. 85±3.70）. Conclusions These findings suggest that the aggregated Aβ-induced microgliosis and neuron apoptosis were similar to those observed in the early phases of Alzheimer disease （AD）, and provide a potential animal model for the study of pathogenesis in the early stages of AD.