降低细胞胆固醇水平对β-淀粉样肽生成的影响  

Effect of cholesterol depletion on the production of β-amyloid

作　　者：王芬[1] 魏翠柏[1] 贾建平[1] 

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《脑与神经疾病杂志》2009年第3期161-164,共4页Journal of Brain and Nervous Diseases

基　　金：国家973基金资助项目(2006CB500700);北京自然科学基金重点资助项目(7071004)

摘　　要：目的观察降低细胞胆固醇水平对β-淀粉样肽(β-amyloid,Aβ)生成的影响,初步探讨胆固醇和阿尔茨海默病(Alzheimer's disease,AD)的相关性。方法以稳定表达人野生型淀粉样前体蛋白(amyloid precursor protein,APP)的神经母细胞瘤SH-SY5Y细胞为模型,分别给予β-甲基环糊精或洛伐他汀对细胞系进行处理;胆固醇定量试剂盒测定细胞内胆固醇水平的变化,放射免疫法测定细胞培养液中Aβ的含量,Western Blot方法半定量检测全长型APP和可溶性APPα的水平。结果β-甲基环糊精和洛伐他汀处理组分别降低细胞胆固醇水平67.5%和49.5%(P<0.05),细胞培养液中Aβ含量分别降低39.5%和25.7%(P<0.05),sAPPα含量分别增加3.5倍和2.0倍(P<0.05)。结论降低细胞胆固醇水平使细胞外Aβ含量减少,sAPPα含量增加,这提示胆固醇可能通过影响APP代谢途径而参与AD的病理过程。Objective To study the effect of cholesterol depletion on the production of β-amyloid （Aβ） and to discuss the role of cholesterol in the pathogenesis of Alzheimer＇s disease （AD）. Methods The SH-SY5Y cells over-expressing wild amyloid precursor protein （APP） were treated by either methyl-β-cyclodextrin （MβCD） or lovastatin. The levels of cholesterol were assayed spectrophotometrically by using the quantitation kit. Aβ concentration was detected by radioimmunity assay, and the levels of holo-APP and α-secretase cleaved soluble APP （sAPPα） were detected by Western Blot. Results Compared with the control group, the cholesterol levels were decreased by 67.5% and 49.5% （P〈0.05） respectively after treatment of MβCD or lovastatin, and Aβ concentrations in culture medium were reduced by 39.5% and 25.7% （P〈0.05） respectively, and the sAPPα levels in culture medium were increased by 3.5 and 2.0 times respectively （P〈0.05）. Conclusion Cholesterol depletion can decrease the level of Aβ and increase the level of sAPPα, which suggest that cholesterol can affect the APP processing and thus involves in the pathogenesis of AD.

关 键 词：Β-淀粉样肽 淀粉样前体蛋白 胆固醇 阿尔茨海默病 

分 类 号：R749.1[医药卫生—神经病学与精神病学]