美金刚对β淀粉样蛋白(下标 25~35)神经毒性的拮抗作用

Objective To investigate the neuroprotective effects of memantine, an excitatory amino acids receptor antagonist, on Aβ(subscript 25-35)-induced cytotoxicity and the possible related mechanisms. Methods Serial concentration of Aβ(subscript 25-35) and memantine were added to PC12 cells, and MTT assays were carried out to detect their effects on cell viability. And effect of Aβ(subscript 25-35) on cell viability of PC12 cells preconditioned with memantine was also detected. The morphological changes of PC12 cells exposured to Aβ(subscript 25-35) and memantine were observed by inverted microscopy. And the effects of memantine on Aβ(subscript 25-35)-induced caspase 3 activation and phospho-protein kinase C (P-PKC) expression were detected by Western blotting. The effects of memantine on Aβ(subscript 25-35)-induced nitric oxide (NO) level and superoxide dismutase (SOD) activity were also measured. Results Aβ(subscript 25-35) could decrease PC12 cells viability in a dose-dependent manner, while pretreatment with memantine could partially antagonize this effect, which was confirmed by morphological observations. Caspase 3 activation and the decreased level of P-PKC induced by Aβ(subscript 25-35) could be attenuated by memantine. Aβ(subscript 25-35) increased NO production and decreased SOD activity, and these effects were partially blocked by pretreatment with memantine. Conclusion Memantine could antagonize Aβ(subscript 25-35)-induced neurotoxicity, which might be one of the therapeutic effect on moderate and severe Alzheimer's disease.