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出 处:《神经疾病与精神卫生》2012年第1期6-8,共3页Journal of Neuroscience and Mental Health
基 金:国家自然科学基金重点资助项目(30830045);国家自然科学基金面上资助项目(81070874);北京市教育委员会科技发展计划项目(KZ201010025023)
摘 要:目的探讨散发型阿尔茨海默病(sporadic Alzheimer’s disease,sAD)患者外周血淋巴细胞中总p53蛋白水平增高,同时出现异常的“突变样”p53表达的可能机制。方法采用诱导AD早期病理改变的重要物质即淀粉样蛋白Aβ25-35刺激健康人外周血淋巴细胞,通过Westernblot检测总p53蛋白及其突变型的表达情况。结果与对照组对比显示,在低浓度(10^-8mol/L)AB2rss作用下,不同时程的淋巴细胞中总p53表达即增高,差异有统计学意义(P〈0.01),并可见微量突变型p53的表达;随着Aβ25-35刺激浓度的提高,总p53水平有增高的趋势,但几乎无统计学意义;突变型p53表达无差异。结论上述结果模拟了sAD患者外周血淋巴细胞中的变化,证实了可溶性Ap在AD发病中的重要作用,以及对p53表达的影响。因而,这一模型将有望在探讨AD的发病机制以及筛选防治AD的药物中发挥一定的作用。Objective To study the possible mechanism of p53 changes, the increased total p53 level and specifically expressed mutant-like p53 in peripheral blood lymphocytes of sporadic Alzheimer's diseases (sAD) patients. Methods Lymphocytes from healthy volunteers were exposed to soluble neurotoxic-amyloid peptide (Aβ25-35)and were evaluated of p53 expression by Western blot analysis. Results Compared with controls, total p53 level was significantly increased (P 〈 0.01) and mutant-like p53 also expressed over time in low doses of amyloid treatment (10-8 mol/l). Meanwhile,although there was a tendency of increased total p53 level as β-amyloid concentration increased, no significant differences were found and no difference in mutant p53 expression. Conclusions All these results were consistent with that found in sAD patients and confirmed the important role of soluble Aβin AD pathogenesis. Thus, this model may play a role in exploring the pathogenesis and medical intervention of AD in the near future.
分 类 号:R749.16[医药卫生—神经病学与精神病学]
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