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

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。

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

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.