GAP-43治疗大鼠脊髓横断后神经中丝NF200表达的变化

The changes of neurofilament 200 expression after GAP-43 therapy on acute complete spinal cord injury rats

通过制备成年SD大鼠完全性脊髓损伤模型,研究生长相关蛋白(GAP-43)治疗大鼠脊髓损伤后神经中丝(NF200)表达的变化,探讨GAP-43在再生修复中的作用,为临床治疗提供实验依据。实验采用雌性8周龄SD大鼠75只,制成脊髓损伤模型后随机分为三组:GAP-43抗体组、GAP-43抗原组和对照组,每组25只。使用直接注射法将GAP-43抗原和GAP-43多克隆抗体分别注入抗原组和抗体组的大鼠脊髓的断端,对照组仅切断脊髓而不给药,最后观察各组大鼠肢体功能的恢复情况。用BBB评分法对不同时段大鼠的行为学表现进行评分,用HE染色及免疫组化染色观察NF200的表达,并对其进行相关性分析。结果发现对照组在不同的时间段行为学评分最低和抗原组评分最高,脊髓损伤区病理改变明显好转,NF200的表达呈进行性增高,且前角神经元NF200的表达早于后角神经元。抗体组早期恢复出现明显的停滞状态,但停药后能很快恢复。说明GAP-43能促进损伤脊髓的恢复,而抗体对损伤脊髓恢复的影响是可逆的,这对于脊髓再生的研究是一种值得探讨的新方法,对进一步探索脊髓损伤的治疗具有重要的意义。

In order to provide evidence for the therapy effect of neuronal factor GAP-43 after spinal cord injury, the expression changes of neurofilament 200 （NF200） in complete spinal cord injury （SCI） rats combined with the behavioral score were observed. Seventy-five 8-week-aged female rats were divided into three groups at random, including GAP-43 antibody therapy group, GAP-43 antigen therapy group and control group with 25 rats in each group. After GAP-43 antibody or antigen being injected into the sectioned sites of the spinal cord, the behavioral scores of the rats were evaluated at different time, while hematoxylin-eosinstain and immunohistochemical staining were used to examine the expression of NF200 in the damaged spinal areas. The results showed that the BBB score was the lowest in the control group and the highest in the antigen group, in which remarkable recovery of pathological changes of spinal cord were observed. Furthermore, in antigen group, the expression of NF200 was increased gradually and NF200 positive neurons in the ventral horn appeared earlier than in the dorsal horn. In antibody groups, early recovery was delayed apparently, but snapped back quickly after discontinuation. The results indicate that GAP-43 has the potent neuroprotective effects in the therapy for spinal cord injury.