腺相关病毒介导β淀粉样肽单链抗体对动物阿尔茨海默病的治疗效果

Therapeutic Effect of Anti-amyloid β Peptide Single-chain Antibody Gene Mediated by Adeno-associated Virus on Animal Alzheimer's Disease

目的观察携带β淀粉样肽单链抗体基因的腺相关病毒对阿尔茨海默病动物模型的治疗效果。方法给突变淀粉样蛋白前体转基因阿尔茨海默病模型小鼠腿部肌肉注射携带Aβ单链抗体基因的腺相关病毒,在药物注射前和注射后3、7、10个月用Morris水迷宫测定潜伏期,并在药物注射后10个月取大脑做组织切片,行免疫组织化学染色,观察淀粉样斑块在海马的沉积。结果注射基因治疗药物后3个月,阿尔茨海默病模型小鼠的学习和记忆能力明显改善,注射基因治疗药物后10个月,模型小鼠海马淀粉样斑块的沉积减少。结论肌肉注射携带Aβ单链抗体基因的腺相关病毒对阿尔茨海默病模型有治疗作用。

Objective To investigate the therapeutic effect of recombinant adeno-associated virus carrying anti-amyloid β peptide single-chain antibody gene on Alzheimer＇s disease（AD） in animal models.Methods The recombinant adeno-associated viruses were injected to the leg muscle of mutant amyloid precursor protein transgenic AD mice.The latency of the mice in Morris water maze was tested before and 3,7,10 months after drug administration.The animal brains were harvested 10 months after drug administration and sectioned for amyloid plaques staining.Results The learning and memory abilities of AD model mice were improved significantly 3 months after gene drug administration.Ten months after gene therapy,the numbers of amyloid plaque in hippocampus of model mice decreased.Conclusion The adeno-associated virus carrying anti-amyloid β peptide single-chain antibody gene has therapeutic effect on AD in model mice.