携带cdc2-siRNA的重组腺相关病毒对C型尼曼-皮克病小鼠行为学的影响  

Effect of recombinant adeno-associated virus encoding cdc2-siRNA on the behavior of Niemann-Pick disease type C mice

作　　者：魏佳军[1] 张旻[1] 卜碧涛[1] 张苏明[1] 徐金枝[1] 王雪贞[1] 降风[1] 郝又国[1] 李丽娟[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,武汉博士研究生430030

出　　处：《卒中与神经疾病》2008年第3期135-138,共4页Stroke and Nervous Diseases

基　　金：国家自然科学基金资助项目(No30400141;No30670737)

摘　　要：目的观察携带cdc2～小干扰RNA（cdc2-siRNA）的重组腺相关病毒（rAAV）小脑注射对C型尼曼-皮克病（NPC）小鼠行为学的影响。方法2周龄npc^-/-小鼠经小脑注射携带cdc2-siRNA的rAAV，动态测量小鼠体重，并进行衣架悬挂实验及足印实验评估小鼠4～8周的运动能力。结果（1）cdc2-siRNA组小鼠体重减轻明显延缓；（2）衣架悬挂实验显示cdc2-siRNA组小鼠运动缺陷明显改善；（3）足印实验显示cdc2-siRNA组相对步距[（75．1±8．6）％]与对照病毒组及非手术组相比明显增加。结论小脑注射携带cdc2-siRNA的rAAV改善了npc^-/-小鼠的行为学，有可能为NPC的治疗提供新的有效途径。Objective To observe the effect of cerebellar injection of recombinant adeno-associated virus （rAAV） encoding cdc2-siRNA on the behavior of Niemann-Pick disease type C （NPC） mice. Methods The rAAV encoding cdc2 siRNA was injected into the cerebellum of 2 weeks old npc^-/- mice. The mice were weighed dynamically and coat hanger test and footprint test were performed to assess their motor ability from 4 to 8 weeks age. Results （1）Weight loss was significantly delayed in cdc2-siRNA group. （2）Coat hanger test showed that the motor defect was remarkably ameliorated in edc2-siRNA group. （3）Footprint test showed that the relative stride in cdc2 siRNA group [（75.1 ± 8.6） %] was markedly longer than that in the controlled viral group and the non surgical group. Conclusions The cerebellar injection of rAAV encoding cdc2-siRNA improves the behavior of npc^-/- mice, which may offer a novel means for treating NPC.

关 键 词：神经元变性 小干扰RNA C型尼曼-皮克病 重组腺相关病毒 

分 类 号：R741[医药卫生—神经病学与精神病学]