bFGF通过抑制Nogo-A信号减少脊髓损伤后胶质瘢痕形成

脊髓损伤后胶质瘢痕的形成是阻碍神经恢复的关键原因之一。碱性成纤维细胞生长因子（basic fibroblast growth factor，bFGF）具有良好的神经保护及促进脊髓损伤的修复作用，然而其对于胶质瘢痕的影响及其机制仍不清楚。本研究通过采用血管动脉夹（30 g）夹闭雌性SD大鼠脊髓2 min造成急性脊髓损伤模型并予以每天皮下注射bFGF（80 μg/kg），探讨bFGF促进脊髓损伤的恢复作用是否涉及到胶质瘢痕调控和Nogo-A/NgR信号的相关机制。通过检测损伤后28 d，各组BBB评分和斜板试验，发现bFGF显著促进脊髓损伤后大鼠运动功能的恢复。HE及尼氏染色显示，bFGF处理组相对于生理盐水处理组，其神经元明显增多，空洞面积减少。同时，星形胶质细胞标记物GFAP免疫荧光结果表明，bFGF减少胶质瘢痕形成，抑制星形胶质细胞过度激活。同样，通过Western 印迹检测发现，bFGF处理后，胶质瘢痕相关蛋白（如GFAP, neurocan）以及神经突生长抑制蛋白（Nogo-A）信号通路相关蛋白质表达量下降。上述结果表明，bFGF可能通过抑制Nogo-A信号蛋白的表达，从而抑制胶质瘢痕的形成，促进脊髓损伤的恢复。此机制研究为脊髓损伤的治疗和恢复提供全新的思路和药物靶点。

bFGF Attenuates the Reactive Astrogliosis by Inhibiting Nogo-A Signaling Pathway after Spinal Cord Injury in Rats

The formation of glial scar after spinal cord injury is one of the key inhibitors of nerve recovery. Basic fibroblast growth factor (bFGF) has a good neuroprotective effect and can promote the recovery of spinal cord injury. However, the role of bFGF in glial scar and its mechanism remains unclear. In this study, we used the vascular artery clamp (30 g) to trap the spinal cord of female SD rats for 2 minutes to induce the acute spinal cord injury model. bFGF (80 μg / kg) was applied subcutaneously every day to evaluate whether bFGF promoted the recovery of spinal cord injury by modulating the glial scar formation and Nogo-A/NgR signaling. bFGF can significantly promote the recovery of motor function in rats after spinal cord injury by BBB score and diagonal plate test in 28 days after injury. H&E and Nissl staining showed that the numbers of neurons in the bFGF treated group were significantly higher than those in the saline treatment group, and the area of the spinal cavity was decreased. Furthermore, immunofluorescence results of astrocyte marker GFAP showed that bFGF could inhbit the formation of glial scar and the overactivation of astrocytes. The expression of GFAP, neurocan and Nogo-A signal pathway-related proteins was decreased after bFGF treatment by Western blotting. These results suggested that bFGF might inhibit the formation of glial scar and suppress the recovery of spinal cord injury by inhibiting the expression of Nogo-A signaling protein. This study provides further understanding for the molecular mechanisms of the recovery of spinal cord injury.