Yue Bin, Lin Yazhou, Ma Xuexiao, Zhang Guoqing, Chen Bohua
Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4593-4598. doi: 10.3892/mmr.2016.5830. Epub 2016 Oct 12.
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.
本研究的目的是利用基因疗法减轻或逆转椎间盘内的退变过程。在本研究中，通过慢病毒载体转染进行生存素基因治疗对兔体内椎间盘退变进程的影响，在体内兔模型中进行了研究。总共15只骨骼成熟的雌性新西兰白兔被随机分为三组：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（C组，n = 5）。根据先前验证的兔椎间盘退变环形切开模型，在L3-L4和L4-L5椎间盘处进行计算机断层扫描引导下的穿刺。3周后，将携带生存素的慢病毒载体注入髓核。结果表明，通过磁共振成像、组织学、基因表达、蛋白质含量和凋亡分析，观察到A组和B组出现椎间盘退变，且随时间增加，两组之间未观察到显著差异（P>0.05）。然而，与穿刺对照组相比，C组的椎间盘退变减轻，差异具有统计学意义（P<0.05）。总体而言，本研究结果表明，将携带生存素的慢病毒载体注入穿刺的兔椎间盘中可延缓与椎间盘退变相关的变化。尽管动物模型的数据外推至人类情况时应谨慎，但本研究提示了基因疗法用于减缓椎间盘退变的潜力。
