摘要
目的 研究兴奋性氨基酸受体拮抗剂美金则（MEM）对β淀粉样蛋白25-35（Aβ25-35）神经毒性的影响及其可能机制。方法 用系列浓度的Aβ25-35和（或）MEM作用PC12细胞，MTT检测其对细胞活力的影响；倒置显微镜下观察细胞形态的变化；Western blotting 检测半胱氨酸蛋白水解酶3（caspase 3）和磷酸化的蛋白激酶C（P-PKC）的表达；检测MEM对Aβ25-35诱导的一氧化氮（NO）产生和超氧化物歧化酶（SOD）活性的影响。结果 Aβ25-35诱导的caspase 3的活化，也可以部分抑制Aβ25-35诱导的P-PKC表达降低。Aβ25-35使NO含量升高，SOD活性下降，预先加入MEM可使NO含量和SOD的活性得到部分恢复。结论MEM可以拮抗Aβ25-35的神经毒性作用，这可能是其治疗中重度阿尔茨海默病的机制之一。
Objective To investigate the neuroprotective effects of memantine, an excitatory amino acids receptor antagonist, on Aβ25-35-induced cytotoxicity and the possible related mechanisms. Methods Serial concentration of Aβ-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-25-35 on cell viability of PC12 cells preconditioned with memantine was also detected. The morphological changes of PC12 cells exposured to Aβ-25-35 and memantine were observed by inverted microscopy. And the effects of memantine on Aβ-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-25-35-induced nitric oxide （NO） level and superoxide dismutase （SOD） activity were also measured. Results Aβ-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-25-35 could be attenuated by memantine. Aβ-25-35 increased NO production and decreased SOD activity, and these effects were partially blocked by pretreatment with memantine. Conclusion Memantine could antagonize Aβ-25-35-induced neurotoxicity, which might be one of the therapeutic effect on moderate and severe Alzheimer＇s disease.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2008年第3期277-280,共4页
Journal of Shanghai Jiao tong University:Medical Science
基金
国家重点基础研究发展规划项目(“九七三”计划)(2006CB500700)
上海市科委基金(04D214005)~~
