三种阿尔茨海默症治疗药物促体外培养小鼠皮层神经元活性的比较

目的:观察并比较3 种阿尔茨海默症治疗药物盐酸美金刚胺、美曲磷酯及白藜芦醇对体外培养小鼠皮层神经元活性的影响, 为寻找作用机理更优的先导化合物提供理论依据。方法:采用体外培养皮层神经元细胞的方法, 解剖分离15 d 胚胎小鼠皮层神经细胞, 接种于96 孔板, 48 h 后加药并培养72 h, 相差显微镜及免疫组织细胞化学方法进行形态学观察, 并以MTT 法观察3 种药物对小鼠皮层神经元活性的影响。结果:盐酸美金刚胺显著促进小鼠皮层神经元活性, 并呈现出一定的量效关系;美曲磷酯10 pmol·L^-1, 0.1, 1, 10 nmol·L^-1 剂量组对皮层神经元细胞活性没有影响, 而美曲磷酯0.1,1 μmol·L^-1剂量组显著抑制皮层神经元细胞活性;0.1 nmol·L^-1白藜芦醇显著促进皮层神经元细胞活性, 而白藜芦醇0.1, 1, 10 μmol·L^-1剂量组显著抑制皮层神经元细胞活性。结论:盐酸美金刚胺促小鼠皮层神经元活性较高, 故以其为先导化合物设计药效更高的阿尔茨海默症治疗药物的方案是可行的。

Comparison of effects of three drugs for Alzheimer's disease on viability of mouse cortical neurons in vitro

AIM: To observe and compare the effects of three drugs for Alzheimer's disease on viability of mouse cortical neurons in vitro including memantine hydrochloride, metrifonate and resveratrol in order to provide experimental data for screening out a better lead compound.METHODS: Mouse cortex neurons were isolated from embryo mice (E15)and plated on 96-well cultureplates with drugs in the serum medium.The effects of different concentrations of drugs on neuron viability were determined by MTT.Phase contrast microscopy and immunocytochemical method were used to examine the influence of drugs on the morphology of the neurons.RESULTS: Memantine hydrochloride enhanced the viability of neurons in a dose dependant way.Metrifonate had no effect but inhibited the effect on the viability of neurons at high concentrations(0.1, 1 μmol·L^-1).Resveratrol enhanced the viability of neurons at low dose (0.1 nmol·L^-1), while inhibited the viability of neurons at high dose(0.1,1, 10 μmol·L^-1).CONCLUSION: It is feasible that memantine hydrochloride can be regarded as the lead compound to design more potential drugs for Alzheimer's disease.