α7神经型尼古丁受体基因抑制对SH-SY5Y细胞Tau和配对螺旋样纤维蛋白1水平的影响  

Influence of inhibited α7 nicotinic acetylcholine receptor gene expression on level of Tau and PHF1 protein in SH-SY5Y cells

作　　者：周飞[1] 张淑丽[1] 李毅[1] 王凡[2] 官志忠[1] 齐晓岚[1] ZHOU Fei ZHANG Shu-Li LI Yi et al(The Key Laboratory of Molecular Biology Laborary, Guizhou Medical University, Guiyang 550004, Chin)

机构地区：[1]贵州医科大学分子生物学重点实验室,贵州贵阳550004 [2]贵州医科大学第一附属医院神经外科

出　　处：《中国老年学杂志》2016年第24期6049-6051,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(81360178);教育部"长江学者和创新团队发展计划资助"(IRT13058);贵州省科技厅重大专项(黔科合重大专项字2014[6008]);贵州省科技厅项目(201344;黔科合J字[2012]2055)

摘　　要：目的探讨α7神经型尼古丁受体(n AChR)基因沉默对SH-SY5Y细胞Tau和配对螺旋样纤维蛋白(PHF)1水平的影响及α7n AChR在阿尔茨海默病(AD)发病机制中的作用。方法 SH-SY5Y细胞转染α7 n AChR shRNA重组质粒,用实时荧光定量PCR和Western印迹法分别测定细胞中α7 n AChR在mRNA和蛋白表达水平的变化;用Western印迹法检测细胞Tau和PHF1蛋白水平。结果α7 n AChR基因沉默组与空质粒组相比,α7 n AChR mRNA和蛋白质表达水平分别降低了94%(P<0.01)和82%(P<0.01);Tau蛋白水平升高了65%(P<0.01);PHF1蛋白水平升高了58%(P<0.05)。结论α7 n AChR基因表达抑制后Tau和PHF1蛋白水平明显升高,Tau蛋白和PHF1蛋白表达增加直接促进神经元纤维缠结的形成,这可能与AD的病理进程有一定关系。Objective To investigate the influence of inhibited gene expression of α7 neuronal nicotinic acetylcholine receptor （nAChR） on the level of Tan and PHF1 proteins in SH-SYSY cells and study the role of α7 nAChR in the pathogenesis of Alzheimer＇s disease （AD）. Methods The level of α7nAChR mRNA and protein were detected by real-time PCR and Western blot, respectively. The protein level of Tau and PHF1 were determined by Western blot. Results Compared with negative controls, the expression of α7nAChR at mR- NA and protein levels in the SH-SYSY cells with α7 nAChR silencing were decreased by 94% and 82%, respectively. And the expression of Tan and PHF1 proteins were increased by 65% and 58%, respectively. Conclusions The inhibited gene expression of α7 nAChR by RNA interference may markedly stimulate the expression of Tan and PHFI proteins, which directly might develop the formation of NFT, so the var- iation of Tan and PHF1 proteins induced by α7 nAChR gene silencing may be related to the pathogenesis of AD.

关 键 词：阿尔茨海默病 TAU 配对螺旋样纤维蛋白1 α7神经型尼古丁受体 

分 类 号：R749.01[医药卫生—神经病学与精神病学]