铁引起认知相关缺损的机制及干预
摘要
目的探讨老年性痴呆等神经退行性疾病患者大脑中神经元烟碱型胆碱能受体(n AchRs)的丢失是否与异常增高的脑铁有关,以及铁神经毒性的作用机制,寻求预防途径。方法建立铁致神经元损伤模型,采用TBARS,MTT,Annexin-V以及配体结合实验方法,观察PC12细胞在铁侵害早期细胞损伤的机制及抗氧化剂的保护作用。结果硫酸亚铁(Fe SO4)在低浓度(1~100μmol/L)范围引起细胞膜脂质过氧化和细胞毒性作用呈剂量依赖性增加,但不引起明显可见的凋亡和坏死。与对照组比较,该浓度范围可引起〔125I〕α-Bungarotoxin结合位点明显减少,但预先用抗氧化剂处理,可阻止铁对〔125I〕α-Bungarotoxin的亲和力。结论铁诱导氧化应激,能降低〔125I〕α-Bungarotoxin结合位点数量,这些改变发生在PC12细胞损害早期阶段。铁与氧化应激对n AchRs的损伤可早于凋亡和坏死的过程,可能发生在神经退行性病程的早期。直接降低脑铁浓度及抑制活性氧化物质的产生应是预防和治疗认知缺损相关神经退行性疾病的一个方向。
引文
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2 车鹏,田建英.α7烟碱型乙酰胆碱受体相关疾病及其研究进展〔J〕.宁夏医科大学学报,2010;32(2):308-11.
3 蒲亚岚,李永红.阿尔茨海默病中枢胆碱能系统的损伤及主要机制〔J〕.中国老年学杂志,2010;30(24):3840-2.
4 王林,史继新.铁的生物特性在神经变性疾病中的作用〔J〕.中国临床康复,2004;8(13):2596-7.
5 姜宏,陈文芳,谢俊霞.帕金森氏综合症模型大鼠脑内多巴胺与铁含量的关系〔J〕.生理学报,2001;53(5):334-8.
6 Enster L.Lipid peroxidation inbiological membranes:mechanisms and implications.In:Yagi K,editor.Active oxygens,lipid peroxidates,and antioxidants〔M〕.Tokyo:Japan Science Society Press,1993:1-38.
7 Rimon G,Bazenet CE,Rubbin LL,et al.Increased surface phosphatidylserine is an early marker of neuronal apoptosis〔J〕.Neurosci Res,1997;48(6):63-70.
8 Kruman I,Guo Q,Mattson MP.Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells〔J〕.Neurosci Res,1998;51(3):293-308.
9 魏艳,谢兆红,许继平,等.阿尔茨海默病生物标记物的研究进展〔J〕.中国老年学杂志,2012;32(15):563-70.
10 Mancuso M,Orsucci D,Siciliano G,et al.Mitochondria,mitochondrial DNA and Alzheimer’s disease.What comes first〔J〕.Curr Alzheimer Res,2008;5(5):457-68.
11 武福军,詹永乐,朱飞奇,等.线粒体变化机制与阿尔茨海默病〔J〕.中国老年学杂志,2011;31(2):354-6.
12 Hellstrom-Lindahl E,Ravid R,Nordberg A,et al.Regional distribution of nicotinic subunit mRNAs in human brain:comparison between Alzheimer and normal brain〔J〕.Brain Res Mol Brain Res,1999;66(4):94-103.
13 Meyer EM,Fiebre CM.3-〔2,4-Dimethoxybenzylidene〕anabasine(DMXB)selsctively activates rat alpha7 receptors and improve memory-related behaviors in a mecamylamine-sensitive manner〔J〕.Brain Res,1997;768(10):49-56.
14 Sano M,Thal LJ,Ernesto C,et al.A controlled trial of selegiline,alphatopopherol,Or both as treatment for Alzheimer disease.The Alzheimer disease cooperative study〔J〕.N Engl J Med,1997;336(17):1216-22.
2 车鹏,田建英.α7烟碱型乙酰胆碱受体相关疾病及其研究进展〔J〕.宁夏医科大学学报,2010;32(2):308-11.
3 蒲亚岚,李永红.阿尔茨海默病中枢胆碱能系统的损伤及主要机制〔J〕.中国老年学杂志,2010;30(24):3840-2.
4 王林,史继新.铁的生物特性在神经变性疾病中的作用〔J〕.中国临床康复,2004;8(13):2596-7.
5 姜宏,陈文芳,谢俊霞.帕金森氏综合症模型大鼠脑内多巴胺与铁含量的关系〔J〕.生理学报,2001;53(5):334-8.
6 Enster L.Lipid peroxidation inbiological membranes:mechanisms and implications.In:Yagi K,editor.Active oxygens,lipid peroxidates,and antioxidants〔M〕.Tokyo:Japan Science Society Press,1993:1-38.
7 Rimon G,Bazenet CE,Rubbin LL,et al.Increased surface phosphatidylserine is an early marker of neuronal apoptosis〔J〕.Neurosci Res,1997;48(6):63-70.
8 Kruman I,Guo Q,Mattson MP.Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells〔J〕.Neurosci Res,1998;51(3):293-308.
9 魏艳,谢兆红,许继平,等.阿尔茨海默病生物标记物的研究进展〔J〕.中国老年学杂志,2012;32(15):563-70.
10 Mancuso M,Orsucci D,Siciliano G,et al.Mitochondria,mitochondrial DNA and Alzheimer’s disease.What comes first〔J〕.Curr Alzheimer Res,2008;5(5):457-68.
11 武福军,詹永乐,朱飞奇,等.线粒体变化机制与阿尔茨海默病〔J〕.中国老年学杂志,2011;31(2):354-6.
12 Hellstrom-Lindahl E,Ravid R,Nordberg A,et al.Regional distribution of nicotinic subunit mRNAs in human brain:comparison between Alzheimer and normal brain〔J〕.Brain Res Mol Brain Res,1999;66(4):94-103.
13 Meyer EM,Fiebre CM.3-〔2,4-Dimethoxybenzylidene〕anabasine(DMXB)selsctively activates rat alpha7 receptors and improve memory-related behaviors in a mecamylamine-sensitive manner〔J〕.Brain Res,1997;768(10):49-56.
14 Sano M,Thal LJ,Ernesto C,et al.A controlled trial of selegiline,alphatopopherol,Or both as treatment for Alzheimer disease.The Alzheimer disease cooperative study〔J〕.N Engl J Med,1997;336(17):1216-22.