Aβ_(1-42)诱导阿尔茨海默病模型大鼠海马内细胞因子表达变化的研究

Changes of Cytokine Expression in the Hippocampus of Aβ_(1-42)-Induced Alzheimer’s Disease Rat Model

目的探讨β淀粉样蛋白(Aβ)1-42诱导的阿尔茨海默病(AD)模型大鼠海马内致炎细胞因子和抗炎细胞因子表达的变化。方法 24只SD大鼠随机分为正常对照组(intact组)、PBS对照组和AD模型组。PBS对照组为海马CA1区注射PBS,AD模型组为海马CA1区注射Aβ1-42。应用Morris水迷宫测试大鼠逃避潜伏期;Nissl染色观察海马CA1区神经元的损害情况;Western blot方法检测海马组织中淀粉样前体蛋白(APP)以及蛋白质磷酸酶-2A(PP2A)的表达量;Real-time PCR法检测海马内细胞因子白介素(IL)-1β、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、IL-4、IL-10和转化生长因子(TGF)-β的mRNA水平。结果大鼠双侧海马内注射Aβ1-42后,动物的空间学习记忆能力降低、海马CA1区神经元胞体丢失、海马内APP表达上调而PP2A表达下调。AD模型大鼠的海马内,致炎细胞因子IL-1β、TNF-α和IFN-γ的mRNA表达上调,而抗炎细胞因子IL-4、IL-10和TGF-β的mRNA表达下调。结论 AD大鼠脑内存在致炎/抗炎失衡的神经炎症,它参与了AD的发病机制。

Objective To explore changes of expression of pro- and anti-inflammatory cytokines in the hippocam- pus of Aβ1-42-induced Alzheimer＇ s disease （AD） rat model. Methods Twenty-four SD rats were divided into control group, PBS group （PBS was injected into CA1 area of hippocampus） and AD model group Aβ1-42 was injected into CA1 area of hip- pocampus）. The escape latency was evaluated by Morris water maze in three groups. Nissl staining was used to detect the le- sions of hippocampal CA 1 neurons. Levels of amyloid precursor protein （APP） and protein phosphatase 2A （PP2A） in hippo- campus were measured by Western blot analysis. Real-time PCR was employed to examine the expressions of pro-inflamma- tory cytokines, including interleukin- 1β （IL- 1β）, tumor necrosis factor- ct （TNF- ct） and interferon- γ （IFN-γ）, and the mRNA expressions of anti-inflammatory cytokines, including IL-4, IL-10 and transforming growth factor-β （TGF-β）. Re- suits Rats subjected to Aβ1-42 injection in bilateral hippocampus led to a ability reduction of learning and memory, a loss of neurons in hippocampus and an increase in the expression of APP, and a decrease in PP2A expression in the hippocampus. In AD hippocampus, The mRNA expressions of the pro-inflammatory mediator, IL-1 [3, TNF-ct and IFN-% were significant- ly up-regulated, but the expressions of the anti-inflammatory cytokines, IL-4, IL-10 and TGF-[~, were markedly down-reg- ulated in AD group compared with those of control and PBS groups. Conclusion The pro-inflammatory/anti-inflammatory imbalance induced neuro-inflammation in AD rats, which was involved in pathogenesis of AD.