淀粉样肽Aβ导致线粒体功能紊乱的体内和体外研究

Research on The Effect of Amyloid beta on Mitochondrial Dysfunction In vivo and In vitro

为探索阿尔茨海默症(AD)中β淀粉样肽(Aβ)对线粒体功能的影响,比较了稳定表达人野生型淀粉样前体蛋白(APP)的细胞和同时转入人Swedish突变APP及ΔE9突变PS1的双转细胞(swe.Δ9)的线粒体功能.结果发现,swe.Δ9细胞的线粒体膜电位、细胞色素c氧化酶活性、线粒体膜流动性、ATP含量均明显低于APP细胞,而APP细胞又明显低于对照的转入空质粒的细胞.在转基因小鼠上也得到类似结果:同时转入人Swedish突变APP和人PS1 M146V敲入的双转小鼠的细胞色素c氧化酶活性和ATP含量比只转入Swedish突变APP的Tg2576小鼠更低.结果证明了AD模型中线粒体功能损害程度与Aβ产量的正相关关系.

To investigate the effect of Aβ on mitochondrial dysfunction,cells stably transfected by human amyloid precursor protein 695（APP） and cells stably co-transfected by familial Alzheimer＇s disease（FAD）-linked Swedish mutant of APP695 gene plus ΔE9 deleted presenilin1 gene（swe.Δ9）were used to study the mitochondrial function.Swe.Δ9 cells showed more reduce in mitochondrial membrane potential,altered complex Ⅳ activity,mitochondrial membrane fluidity and ATP content.However,these parameters in APP cells were lower than those in N2a cells stably transfected with empty vector.The similar results were observed in transgenic mice.APP/PS1M146V/＋ mice showed more reduced complex Ⅳ activity and ATP content than Tg2576 mice.These data indicated that the dose-dependent effect of Aβ on mitochondrial dysfunction.