目的：研究硒、锌干预对体外淀粉样前体蛋白（amyloid precursor protein，APP）酶解通路的影响。方法用0.1μmol/L的硒、锌处理胚鼠皮层神经元细胞，采用酶联免疫吸附测定法（enzyme linked immunosorbent assay，ELISA）检测γ-内切酶活性；另用脂质体转染构建 APP695高表达 CHO 细胞系,用 G418(500mg/L)对转染后细胞进行筛选，最终获得表达人CHO-APP695细胞模型，Western-blot法检测APP-N端片段蛋白的表达。用0.1μmol/L的硒、锌处理转染细胞，48h 后，ELISA 法检测细胞培养上清中 Aβ1-40含量，Western-blot 法检测细胞裂解液 APP-N 端片段蛋白的表达。结果 Western-blot法检测显示CHO-APP695细胞高表达APP-N端片段蛋白；与对照组比较，硒、锌处理组抑制内源性γ-内切酶的活性，且硒、锌联合使用，抑制作用增强；Aβ1-40的含量也减少；单纯硒、锌和硒锌联合处理组， APP-N端片段蛋白表达水平增加。结论硒、锌抑制内源性γ-内切酶对APP蛋白的剪切，减少Aβ1-40的生成，可能对阿尔茨海默病的发病及进展有一定的预防保护作用。“,”Objective To study the effects of selenium and zinc on amyloid precursor protein (APP) in senile dementia model cell.Method 0.1μmol/L selenium and 0.1μmol/L zinc were added to primary cultured hippocampus neuron cells isolated from fetal rats. The activity ofγ-secretase was measured by enzyme-linked immunosorbent assay (ELISA). In addition, the APP695 gene was transfected into CHO cells and stably transfected cell clones were screened by G418 (500mg/L).After treatment with selenium and zinc for 48h, the APP-N terminal fragment protein expression was identified by Western-blot analysis and Aβ1-40concentration was detected by ELISA in the supernatants of cell culture. Results Western-blot assay showed highly expression of APP-N terminal fragment protein in CHO-APP695 cells, indicating that the APP695-overexpression CHO cell line was established. Compared with control group, the results of ELISA analysis showed that selenium and zinc could inhibit the activity ofγ-secretase, and the combination of selenium and zinc could decrease the concentration of Aβ1-40 more significantly. Selenium, zinc combination of selenium and zinc increased the APP-N terminal fragment protein expression.Conclusion Selenium and zinc have potential protection against Alzheimer’s disease by inhibiting the activity ofγ-secretase and decreasing Aβ1-40 production.