5-取代-1-氮杂蒽酮类衍生物A7对APPsw细胞分泌Aβ_(1-42)蛋白的抑制作用研究

Inhibition Effect of 5-Substituted 1-Nitrogen Anthracene Ketone Derivatives A7 on Aβ_(1-42) Protein Secretion in APPsw Cells

目的:探讨5-取代-1-氮杂蒽酮类衍生物对过表达APPsw的SH-SY5Y细胞(简称APPsw细胞)分泌Aβ_(1-42)蛋白的影响。方法:将APPsw细胞分为四组,分别为对照组(只加入溶剂)、高剂量组(10μmol·L^(-1)衍生物)、中剂量组(1μmol·L^(-1)衍生物)、低剂量组(0.1μmol·L^(-1)衍生物)。MTT法检测细胞存活率,ELISA测定细胞外Aβ_(1-42)水平;Western Blot检测Aβ_(1-42)前体蛋白APP的表达变化。结果:5-取代-1-氮杂蒽酮类衍生物中化合物A7可剂量依赖性增加细胞活力;ELISA和Western blot结果显示,A7可剂量依赖性减少APPsw细胞外Aβ_(1-42)蛋白水平和前体蛋白APP表达,高剂量A7可使显著性下调Aβ_(1-42)蛋白分泌(P<0.05),降低前体蛋白APP表达(P<0.05)。结论:5-取代-1-氮杂蒽酮类衍生物A7可以抑制APPsw细胞中Aβ_(1-42)蛋白的表达。

Objective： To investigate the effect of 5-substituted l-nitrogen anthracene ketone derivatives on the Aβ1-42 secrelion in SH-SY5Y cells with overexpressing APPsw （APPsw cells）. Methods： The APPsw cells were divided into four group （ only adding the solvent with equal concentration）, and the derivatives groups respectively at high （ 10 mol· L-1） , medi- um （ 1 mol · L-1 ） and low （ 0. 1 mol · L-1 ） dose. The cell viability of each group was deieeted by MTT, the level of llular Aβ1-42 was assessed by ELISA, and Western blot was used to assess the changes in the expression of Aβ1-42 premusor protein APP. Results： The compound A7 of 5-substituted 1 -nitrogen anthracene ketone derivatives improved the activity of cells in a dosemanner; ELISA and Western blot revealed that A7 reduced the expression of Aβ1-42 extracellular Aβ1-42 precursor protein APP in a dose-dependent manner, the high dose of A7 reduced the expression of Aβ1-42 significanlly （P 〈0. 05）, and decreased the expressiou Aβ1-42 precursor protein APP （P 〈0.05）. Conclusion： A7 as one of 5-substituted 1-nimgen antluaeer ketoue derivatives it the secretion of Aβ1-42 in APPsw cells.