单体、寡聚体及纤维状Aβ毒性作用的比较研究

Comparison study of neuronal toxicity with Monomers,oligomers and fibrillar Aβ

目的采用Alzheimer’s disease(AD)动物模型,阐明单体与寡聚体Aβ对神经细胞毒性作用。方法本实验孵育获得寡聚体及纤维状Aβ,采用核黄素标记光度法测定Aβ凝聚度。采用寡聚体Aβ损伤大鼠海马CA1区来制备AD大鼠模型,并采用流式细胞术法检测AD大海马细胞凋亡情况。结果寡聚体Aβ神经毒性比单体及纤维化Aβ组,海马含亚G1期细胞百分数明显增多;寡聚体Aβ组与单体及纤维化Aβ组相比较具有显著性差异。结论寡聚体Aβ神经毒性比单体及纤维状Aβ更加显著,寡聚体Aβ可导致神经细胞凋亡,神经细胞凋亡参与了AD的发病。

Objective To study the role the neuronal apoptosis in Alzheimer＇s disease（AD）using the rat model.Methods Monomeric Aβ,oligomeric Aβ and fiber Aβ was stereotaxically injected into the hippocampus to establish the rat model of AD,the percentage of apoptotic cell in hippocampus were measured by flow cytometry.Results The percentage of apoptotic cell in the hippocampus of oligomeric Aβ were significantly increased.However,toxicity in hippocampal neuron did not correlation with level of Aβ agglomeration.Furthermore,Aβ fibrosis decreased Aβ toxicity.Conclusion The neuronal damage by oligomeric Aβ induced the cellular apoptosis.These results further support the oligomeric Aβ play a key role in the occurrence of AD.