核转录因子及炎性趋化因子在阿尔茨海默病患者脑组织中的改变

目的 探讨核转录因子(NF) -κBp65、炎性趋化因子单核细胞趋化蛋白1(MCP-1/CCL-2)、巨噬细胞炎性蛋白-1α(MIP-1 α/CCL-3)和胶质纤维酸性蛋白(GFAP)等在阿尔茨海默病(AD)发病中的改变。方法 选择尸体解剖后的10例AD患者及8例对照脑组织,用免疫组织化学EnVision方法检测海马、大脑额叶及颞叶皮质中NF-κBp65、MCP-1、MIP-1α、GFAP和Aβ1-42的表达。结果 与对照组相比,AD患者脑组织海马、额叶和颞叶皮质等部位均显示神经细胞中NF-κBp65每高倍视野(×400)阳性细胞数分别为3.6±1.5、2.2±1.2和2.2±1.2]表达较对照组（每高倍视野阳性细胞数分别为0.31±0.20、0.25±0.20和0.25±0.20）明显增高(P＜0.05);MCP-1及MIP-1α在海马、额叶和颞叶皮质等部位神经细胞中（每高倍视野阳性细胞数分别为8.0±1.3、8.8±1.0、9.3±1.4;及8.1±1.5、12.5±1.1、6.4±1.1）表达均较对照组（每高倍视野阳性细胞数分别为4.5±0.9、4.5±0.6、4.0±1.8;及5.0±1.9、6.3±2.2、3.8±1.5）明显增多(P＜0.05);GFAP显示的星形胶质细胞数增多(P＜0.05),并大量聚集在老年斑周围。相关系数分析表明,在AD脑组织中MCP-1、MIP-1α蛋白水平与NF-κBp65的改变有关。结论 AD脑组织中核转录因子及炎性趋化因子表达升高,NF-κBp65可能调节MCP-1和MIP-1α的表达,其机制可能与Aβ引起的炎性作用有关。

Changes of nuclear factor and inflammatory chemotactic factors in brain of patients with Alzheimer's disease

Objectives To investigate the changes of nuclear factor (NF-) κBp65 and inflammatory chemotactic factors including monocyte chemoattractant protein 1 (MCP-1/CCL-2), macrophage inflammatory protein 1α (MIP-1α/CCL-3), glial fibrillary acidic protein (GFAP) in brains of the patients with Alzheimer's disease (AD) and reveal the correlation of these factors. Methods Ten patients with AD and 8 age-matched control subjects were selected in the study. Immunohistochemistry was performed to determine the protein expression of NF-κBp65, MCP-1, MIP-1 α and GFAP. Double-immunohistochemistry was used to detect the expression of GFAP and β-amyloid peptide 1-42 ( Aβ1-42 ) in the hippocampus,temporal and frontal cortices. Results As compared to age-matched controls ( the numbers of the positively stained neuronal cells: 0.31 ±0. 20, 0. 25 ±0.20 and 0. 25 ±0. 20, respectively), the immunoreactivities of NF-κBp65 in the hippocampus and the temporal and frontal cortices ( numbers of the positively stained cells: 3.6 ± 1.5, 2. 2 ± 1.2 and 2. 2 ± 1.2, respectively) were significantly increased in AD brains. The levels of MCP-1 and MIP-1α in the hippocampus, and the temporal and frontal cortices ( numbers of the positively stained neuronal cells: 8. 0 ± 1.3, 8. 8 ± 1. 0, 9. 3 ± 1.4, respectively;and 8. 1 ± 1. 5, 12. 5 ±1.1, 6.4 ± 1. 1, respectively) with AD were significantly higher than those of controls ( the numbers of the positive neuronal cells : 4. 5 ± 0. 9, 4. 5 ± 0. 6, 4. 0 ± 1.8, respectively; and 5.0 ± 1.9, 6. 3 ± 2. 2, 3. 8 ±1.5, respectively). An increased number of glial cells stained with GFAP were observed to extensively distribute around the senile plaques in AD brains. There were significant correlations between NF-κBp65 and these inflammatory chemotactic factors in AD brains. Conclusion Correlative expressions of NF and inflammatory chemotactic factors were found in the brains of AD patients, through a mechanism that may involve the inflammatory response induced by Aβ in the processing of AD.