中文摘要：

目的 研究五味子乙素抑制M146L细胞Aβ42生成的机制。方法 体外培养高效表达Aβ42的M146L细胞株，分别加入不同浓度的五味子乙素（1．67，5．00和15．00μg·mL6-1）、β分泌酶抑制剂（S4562，100．00μg·mL^-1）和γ分泌酶抑制剂（S2188，13．68μg·mL^-1）。用CCK-8（cell counting kit-8）比色法检测不同处理对M146L细胞活性的影响；用ELISA法测定M146L细胞所分泌的Aβ42的变化；用Westernblotting检测APP的β分泌酶剪切产物C99蛋白的含量变化，结合用β和γ分泌酶活性试剂盒，检测五味子乙素对这两种酶活性的影响。结果不同处理因素对M146L细胞的存活率均无影响，不具有细胞毒作用。中、高剂量的五味子乙素均不同程度地抑制M146L细胞分泌Aβ42及γ分泌酶的活性，但都不改变M146L细胞C99蛋白的含量及β分泌酶的活性。结论 五味子乙素可抑制γ分泌酶活性，其降低Aβ42生成是通过抑制γ分泌酶的活性来实现的。

英文摘要：

Aim To investigate the inhibition of amyloidβ-protein 42 （Aβ42） production in M146L cells by γ-schisandrin. Methods M146L cells which can produce considerable Aβ42 in vitro were treated with γ-schisandrin （ 1.67, 5.00 and 15.00 μg · mL^-1 ） , β-secretase inhibitor （ S4562, 100.00 μg ·mL^-1） and γ-secretase inhibitor （S2188, 13.68 μg · mL^-1）, separately. Cell counting kit-8 （CCK-8） was used to assess cell viability. Enzyme-linked immunosorbent assay （ELISA） was carried out to determine the amount of Aβ42. Western blotting was used to examine C99, an intermediary product of APP cleaved by β-secretase. β-Secretase and γ-secretase activities were assayed by commercial kits. Results The CCK-8 assay indicated that different concentrations of γ-schisandrin had no neurotoxicity on the cultured M146L. And the ELISA test showed that the amount of Aβ42 secreted by M146L ceils treated with γschisandrin （5.00 and 15.00 μg · mL^-1） decreased obviously as compared with solvent control. The results of Western blotting test indicated that there was no change of C99 contents and β-secretase activity in β-schisandrin treated ceils, while γ-secretase activity decreased obviously. Conclusion γ-Schisandrin inhibited production of Aβ42 in M146L ceils through inhibiting γ-secretase.