cdk5反义寡核苷酸治疗NPC小鼠神经元变性的实验研究  

Treatment of Neurodegeneration in NPC Mice by cdk5 Antisense Oligonucleotides

作　　者：潘邓记[1] 夏文广[2] 杨业新[3] 朱舟[1] 张旻[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]湖北省新华医院康复科,武汉430015 [3]中国地质大学(武汉)医院,武汉430030

出　　处：《中国康复》2008年第3期155-157,共3页Chinese Journal of Rehabilitation

基　　金：湖北省自然基金(2006ABA124);国家自然科学基金(30400141;30670737)

摘　　要：目的:研究cdk5反义寡核苷酸(ASODN)对C型Niemann-Pick病小鼠神经元变性的影响。方法:以NPC小鼠为动物模型,共30只,分为对照组和干预组各15只,分别予侧脑室持续灌注人工合成cdk5寡核苷酸的正义链(SODN)和ASODN,共2周,利用染色及免疫荧光染色、免疫印迹技术观察2组cdk5表达水平、神经元细胞骨架蛋白磷酸化水平、轴突球状体及存活浦肯野神经元数目,并进行动物行为学评定。结果:灌注反义cdk5的干预组与对照组比较cdk5的表达、减低神经元细胞骨架蛋白磷酸化指标SMI31、PHF-1在脑部的表达水平及病理性球状神经轴突数量均明显降低,神经元存活率及小鼠的运动功能均明显提高(均P<0.05)。结论:反义cdk5能降低NPC神经元细胞骨架的损伤和变性,从而改善NPC小鼠运动功能的缺失。Objective： To investigate the effect of cdk5 antisense oligonucleotides on neurodegeneration in NPC mice. Methods： The Balb/c nih npc-1 mice were randomly divided into control and treatment groups （n= 5 in each group）. Sense or antisense oligonucleotides were respectively infused into 4-week-old npc mice intracerebroventricularly for a 2-week period in control group or treatment group. H＆E staining,immunohistochemistry,immunofluorescence staining and Western bolt were used to detect the expression of cdk5, hyperphosphorylation of cytoskeletal proteins, axonal spheroid and Purkinje neuron number,and mouse coat hanger test was adopted to evaluate the motor function of npc mice. Results： The expression levels of cdk5,SMI31,PHF-1 and the number of axonal spheroids in NPC mice were decreased significantly,and motor defects were ameliorated significantly in treatment group. Conclusion： cdk5 antisense oligonucleotides can ameliorate the injury and degeneration of neuron cytoskeleton and the deficit of motor function in npc mice.

关 键 词：反义寡核苷酸 周期素依赖性蛋白激酶5 神经元变性 轴突球状体 

分 类 号：R96[医药卫生—药理学]