Humanin对实验性阿尔茨海默病小鼠海马小胶质细胞OX-42表达的影响

Effect of Humanin on microglia OX-42 expression in experimental Alzheimer¢s disease mice

摘要:

目的 探讨Humanin（HN）在体内是否存在对实验性阿尔茨海默病（AD）小鼠的神经保护作用以及可能的机制。方法 采用β-淀粉样蛋白（Aβ）脑内注射方法建立AD模型。健康雄性小鼠60只, 随机分为假手术组（n = 15）、Aβ模型组（n = 15）和HN治疗组（n = 30）。应用免疫组织化学方法于造模后3, 7, 14 d观察海马小胶质细胞OX-42表达的变化; Nissl染色方法检测3组动物海马区病理改变。结果 OX-42免疫组织化学染色显示, 与Aβ模型组比较, HN治疗组造模后3, 7, 14 d海马OX-42阳性细胞的表达均减少（P＜0.05）; Aβ模型组、HN治疗组在手术后各时间点Nissl染色均可见海马区病理改变, HN治疗组在相同时间点炎性的病理变化弱于Aβ模型组。结论 在活体内, HN可以减少Aβ25~35毒性引起的OX-42的表达, 具有神经保护作用。

Abstract:

Objective To investigate whether Humanin (HN) has an in vivo neuroprotective effect on experimental mice with Alzheimer′s disease (AD) and the possible mechanism. Methods AD models were established by intracerebral injection?of β-amyloid?protein (Aβ). A total of 60 healthy male mice were randomly divided into 3 groups: sham operated group (n = 15), Aβ model group (n = 15) and HN treatment group (n = 30). Changes in expression of OX-42 in hippocampal region were observed by the immunohistochemical method on 3,7,14 days after modeling. Nissl staining was performed to detect the pathological changes of the hippocampal region of different groups of animals. Results The number of OX-42 positive cells in hippocampal region was reduced in HN treatment group on 3,7,14 days (P＜0.05). Pathological changes of the hippocampal region were detected by Nissl staining in both Aβ model group and HN treatment group after surgery, but the inflammatory changes of HN treatment group were less than Aβ model group at each time point. Conclusion In vivo, HN can reduce the expression of OX-42 induced by the toxicity of Aβ25-35 which proved that HN has neuroprotective effect.