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Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model

机译:慢病毒载体存活蛋白基因治疗对体内兔模型椎间盘退变过程的影响

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摘要

The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.
机译:当前研究的目的是使用基因疗法来减轻或逆转椎间盘内的退行性过程。在当前的体内兔模型研究中,研究了通过慢病毒载体转染的survivin基因治疗对椎间盘退变过程的影响。将总共​​15只骨骼成熟的雌性新西兰白兔随机分为三组:穿刺空白对照组(A组,n = 5),穿刺空载体对照组(B组,n = 5)和治疗组(组)。 C,n = 5)。根据先前验证的用于椎间盘退变的兔瓣环切开术模型,在L3-L4和L4-L5椎间盘上进行计算机断层扫描引导的穿刺。 3周后,将携带存活蛋白的慢病毒载体(LV)注射到髓核中。结果表明,通过磁共振成像,组织学,基因表达,蛋白含量和细胞凋亡分析,观察到A,B组椎间盘退变,随时间增加,两组间差异无统计学意义(P> 0.05)。 )。然而,与穿刺对照组相比,C组的椎间盘退变减少了,差异具有统计学意义(P <0.05)。总体而言,本研究的结果表明,将带有存活蛋白的LV注射到穿刺的兔椎间盘中,可以延迟与椎间盘退变相关的变化。尽管应该谨慎地将动物模型中的数据外推至人体状况,但本研究表明,使用基因治疗来降低椎间盘退变的潜力。

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