官志忠,田茂萍,肖雁
GUAN Zhizhong1,2,TIAN Maoping1

• 1:贵阳医学院病理学教研室
• 2:贵阳医学院分子生物学重点实验室
• 3:贵阳市妇幼保健院

摘要(Abstract)：

目的:研究胆固醇降解药辛伐他汀(Simivastatin)对SH-SY5Y神经细胞中胆碱能神经的刺激作用,探讨史他汀类药物在神经退变性疾病中的神经性保护机制。方法:体外培养SH-SY5Y神经细胞(源于人神经母细胞瘤细胞),在培养液中加入辛伐他汀培养48h,然后用比色法测定细胞MTT还原率及胆碱酯酶活性,用蛋白印迹方法测定尼古丁受体α7和α3蛋白水平,RT-PCR方法测定该类受体mRNA表达水平。结果:辛伐他汀能降低培养细胞中乙酰胆碱酯酶和丁酰胆碱酯酶活性(分别降低41.9%和18.1%);增强尼古丁受体α7亚单位的蛋白和mRNA表达水平(分别升高23%和32%),但对α3无明显影响。结论:辛伐他汀可以刺激胆碱能神经系统,可能具有神经性保护作用。
Objective:To investigate the effect of simivastatin on cholinergic nerve system and to understand neuroprotective mechanisms of the drug in neurodegenerative diseases. Methods:SH-SY5Y cells (human neuroblastoma cell line),were incubated with simivastatin for 48 hr. The MTT reduction and cholinesterase activity were measured by using photometric method; the expressions of nicotinic acetylcholine receptor (nAChR)subunits α7 and α3 at protein and mRNA levels were detected with Western blotting and RT-PCR techniques respectively. Results:Simivastatin inhibited the activities of acetylcholinesterase and butyrylcholinesterase by 41.9% and 18.1%,respectively,in the cultured cells. The drug increased the expressions of nAChR α7 at both protein and mRNA levels by 23% and 32%,respectively; however,it dose not induce any changes in the expression of nAChR α3. Conclusions:Simivastatin can stimulate the cholinergic nervous system and may play certain neuroprotective effects.

关键词(KeyWords)： 辛伐他汀;胆碱酯酶类;尼古丁受体;SH-SY5Y神经母细胞瘤细胞
Simivastatin; cholinesterases; receptors,nicotine; SH-SY5Y cells

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(30870986);; 科技部国际合作基金资助项目(2006DFA3353)

作者(Author): 官志忠,田茂萍,肖雁
GUAN Zhizhong1,2,TIAN Maoping1

DOI: 10.19367/j.cnki.1000-2707.2008.06.004

参考文献(References)：

• [1]Puglielli L,Tanzi RE,Kovacs DM.Alzheimer's disease:the cholesterol connection[J].Nat Neurosci,2003(4):345-351.
• [2]Wood WG,Schroeder F,Igbavboa U,et al.Brain mem-brane cholesterol domains,aging and amyloid beta-pep-tides[J].Neurobiol Aging,2002(5):685-694.
• [3]Vaughan CJ,Murphy MB,Buckley BM.Statins do more than just lower cholesterol[J].Lancet,1996(9034):1079-1082.
• [4]Liu Y,Peterson DA,Kimura H,et al.Mechanism of cel-lular3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoli-um bromide(MTT)reduction[J].J Neurochem,1997(2):581-593.
• [5]Darreh-Shori T,Almkvist O,Guan ZZ,et al.Sustained cholinesterase inhibition in AD patients receiving rivastig-mine for12months[J].Neurology,2002(4):563-572.
• [6]Guan ZZ,Zhang X,Mousavi M,et al.Reduced expres-sion of neuronal nicotinic acetylcholine receptors during the early stages of damage by oxidative stress in PC12cells[J].J Neurosci Res,2001(4):551-558.
• [7]Hellstrom-Lindahl E,Mousavi M,Zhang X,et al.Regional distribution of nicotinic receptor subunit mRNAs in human brain:comparison between Alzheimer and normal brain[J].Brain Res Mol Brain Res,1999(1-2):94-103.
• [8]官志忠,齐晓岚.阿尔茨海默病的分子发病机制及其治疗研究进展[J].中华病理学杂志,2008(1):11-15.
• [9]Jick H,Zornberg GL,Jick SS,et al.Statins and the risk of dementia.Lancet,2000(9242):1627-1631.
• [10]Xiu X,Nordberg N,Shan KR,et al.Lovastatin stimu-lates up-regulation of alpha7nicotinic receptors in cul-tured neurons without cholesterol dependency,a mecha-nism involving production of the alpha-form of secreted amyloid precursor protein[J].J Neurosci Res,2005(4):531-541.
• [11]Paterson D,Nordberg A.Neuronal nicotinic receptors in the human brain[J].Prog Neurobiol,2000(1):75-111.

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