天津医药

• 实验研究 •    下一篇

Aβ1-42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

张雪梅1,柯开富2,方小霞1,邱一华1,彭聿平1   

  1. 1. 南通大学医学院生理学系
    2. 南通大学附属医院神经内科
  • 收稿日期:2012-12-18 修回日期:2013-05-08 出版日期:2013-08-15 发布日期:2013-08-15
  • 通讯作者: 彭聿平

Changes of Cytokine Expression in the Hippocampus of Aβ1-42-Induced Alzheimer’s Disease Rat Model

ZHANG Xuemei 1,KE Kaifu 2,FANG Xiaoxia 1,QIU Yihua 1,PENG Yuping 1   

  1. 1. Department of Physiology, School of Medicine, Nantong University， Natong 226001, China
    2. Department of Neurology, Affiliated Hospital of Nantong University
  • Received:2012-12-18 Revised:2013-05-08 Published:2013-08-15 Online:2013-08-15
  • Contact: PENG Yuping

PDF (PC)

2202

摘要： 【摘要】 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。

关键词: 阿尔茨海默病, 海马, 淀粉样β蛋白, 淀粉样β蛋白前体, 蛋白质磷酸酶2, 细胞因子类, 大鼠, SpragueDawley

Abstract: Objective   To explore changes of pro- and anti-inflammatory cytokines expression in the hippocampus of Aβ1-42- induced AD rat model. Methods   Sprague Dawley rats (200 ± 20 g) were injected Aβ1-42 , the escape latency was evaluated by Morris water maze. Lesion of neurons within the hippocampus CA1 area was detected by Nissl staining. The levels of amyloid precursor protein (APP) and protein phosphatase 2A (PP2A) in hippocampus were measured by means of Western blot analyses. Real-time PCR was employed to examine the expressions of pro- inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and anti-inflammatory cytokines including IL-4, IL-10, transforming growth factor-β (TGF-β). Results   Rats subjected to Aβ1-42 injection within bilateral hippocampus confirmed the success to make AD rat models, which led to reduction of the ability of learning and memory; Nissl staining showed pyramidal cells disturbed, neurons decreased significantly. the treatment with Aβ1-42 notably increased expression of APP but decreased PP2A expression level. There was evidently up-regulation in the expressions of pro-inflammatory mediator mRNAs in AD rats, including IL-1β, TNF-α and IFN-γ. Contrarily, the expressions of anti-inflammatory cytokine mRNAs, including IL-4, IL-10 and TGF-β, were significantly down-regulated relative to the control rats. Conclusions   Aβ1-42 injection in bilateral rat hippocampus induces AD model. Neuroinflammation resulting from pro- and anti-inflammatory unbalance is involved in pathogenesis of AD.

Key words: Alzheimer's disease, hippocampus, amyloid beta-protein, amyloid beta-protein precursor, protein phosphatase 2, cytokines, cytokines, SpragueDawley