腺病毒介导脑源性神经营养因子基因转移对神经根损伤后神经元的保护和促轴突再生作用

Effects of adenovirus-mediated brain-derived neurotrophic factor gene transfer on neruon protection and neurite regeneration after nerve root injury

目的 探讨腺病毒向脊髓内转移脑源性神经营养因子 (BDNF)基因能否在脊髓水平修复神经根损伤。 方法 在大鼠神经根切断吻合模型基础上 ,通过显微注射法在立体定位仪上将 2 μl复制缺陷型重组腺病毒载体 (AxCA -BDNF)直接注入大鼠神经根损伤部相应的脊髓腹角。观察伤后脊髓尼氏染色神经元和轴突计量及形态学改变。 结果 与单纯损伤组比较 ,注射AxCA -BDNF可明显增加神经根伤后尼氏染色阳性神经元的百分率、有髓神经纤维数目以及髓鞘厚度。 结论 神经根重建结合BDNF基因治疗可明显减少神经根伤后尼氏染色神经元的死亡以及促进轴突再生 。

Objective To investigate whether recombinant adenovirus mediated brain derived neurotrophic factor (BDNF) gene can repair nerve root injury (NRI) at the spinal cord level by transferring it into spinal cord. Methods Based on nerve root transection and reanastomosis model, 2 μl of recombinant adenovirus vector (AxCA BDNF) and virus buffer was transferred into spinal ventral horn through microinjection in a stereotaxic frame. Morphological changes of Nissle stained neurons and regenerated neurites were observed after NRI. Results AxCA BDNF gene transfer increased the percentage of Nissle stained neurons, the number of neurites and the thickness of myelin significantly. Conclusions Nerve root reconstruction combining with BDNF gene therapy can significantly decrease neuronal death and promote the neurite regeneration. This study provides a new and effective treatment for NRI at the level of spinal cord.