bFGF通过抑制Nogo-A信号减少脊髓损伤后胶质瘢痕的形成

发布时间：2018-04-27 05:16

本文选题：脊髓损伤 + 碱性成纤维细胞生长因子　；参考：《中国生物化学与分子生物学报》2017年07期

【摘要】：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2min造成急性脊髓损伤模型并予以每天皮下注射bFGF(80μg/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。
[Abstract]:The formation of glial scar after spinal cord injury is one of the key factors hindering nerve recovery. Basic fibroblast growth factor-bFGFs have a good neuroprotective effect and promote the repair of spinal cord injury. However, the effect of basic fibroblast growth factor on glial scar and its mechanism are still unclear. In this study, the acute spinal cord injury model of female SD rats was induced by 30 g occlusion of vascular artery clamp. BFGF(80 渭 g / kg was injected subcutaneously every day to investigate whether the effect of bFGF on the recovery of spinal cord injury was related to glial scar regulation and glial scar regulation. The related mechanism of Nogo-A/NgR signal. On the 28th day after injury, the BBB score and inclined plate test showed that bFGF significantly promoted the recovery of motor function in rats after spinal cord injury. He and Nissl staining showed that the neurons in the treated group were significantly higher than those in the saline group. The void area is reduced. At the same time, GFAP immunofluorescence results showed that bFGF decreased the formation of glial scar and inhibited the excessive activation of astrocytes. Similarly, Western blotting showed that the expression of signal transduction related proteins in glial scar associated proteins (such as GFAPN neurocanand and neuronal growth inhibitory protein Nogo-A) decreased after treated with bFGF. These results suggest that bFGF may inhibit the formation of glial scar and promote the recovery of spinal cord injury by inhibiting the expression of Nogo-A signal protein. This study provides new ideas and drug targets for the treatment and recovery of spinal cord injury.
【作者单位】：南昌大学附属第二医院麻醉科;温州医科大学药学院分子药理研究中心;浙江省宁波市李惠利医院药剂科;江西中医药大学附属第二医院麻醉科;
【基金】：江西省重点研发计划(No.20161BBG70212) 宁波市自然科学基金(No.2015A610208)资助~~
【分类号】：R651.2

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