Objective: To investigate the effects of AG1478, an EGFR inhibitor, on the microenvironment of axonal regeneration after spinal cord injury (SCI). Methods: Sixty SD rats were randomly divided into the groups AG1478, control and the sham (n=20 respectively). Allen weight drop technique was used to make injury models. The SCI on rats was caused with 10 g×1.25 cm impact injury at T10. Then the rats in the AG1478 group were administrated locally with AG1478 while the rats in the sham and control groups were administrated with dimethylsulfoxid instead. The expressions of phosphorylated epidermal growth factor receptor (pEGFR), glial fibriliary acidic protein (GFAP), chondroitin sulphate proteoglycan (CSPGs) and growth associated protein-43 (GAP-43) at days 7 and 14 after SCI were measured. The neural functions and the body weight recovery were observed at day 1, and weeks 1, 2, 4, 6 and 8 after SCI. Results: The expressions of pEGFR, GFAP and CSPGs in the AG1478 group were significantly lower than that in the control group (P< 0.01), while the expression of GAP-43 in the AG1478 group was significantly higher than that in the control group (P< 0.01). The BBB scores in the AG1478 group were significantly higher than that in the control group (P< 0.01) and the body weight in the AG1478 group increased more quickly than that in the control group (P< 0.05). Conclusion: Administration of AG1478 promotes the neural functions recovery by improving the microenvironment of axonal regeneration after SCI.%目的:研究表皮生长因子受体(EGFR)抑制剂AG1478 对脊髓损伤后突触再生微环境的影响.方法:SD 大鼠60 只随机分为AG1478 组、对照组和假手术组.AG1478 组和对照组采用重物坠落打击法建立大鼠脊髓损伤模型,假手术组仅暴露硬脊膜,不损伤脊髓;AG1478 组在脊髓损伤局部给予AG1478 治疗,对照组和假手术均给予二甲基亚砜作对照治疗.于术后14 及28d,观察各组大鼠脊髓损伤后磷酸化表皮生长因子受体(pEGFR )、硫酸软骨素蛋白多糖(CSPGs )、胶质纤维酸性蛋白(GFAP )、生长相关蛋白43(GAP-43)的表达;于术后1d 及1、2、4、6、8 周,观察各组大鼠神经功能恢复和体重变化的差异.结果:AG1478 组pEGFR 、CSPGs 和GFAP 的表达明显低于对照组(P＜0.01),而GAP-43 的表达明显高于对照组(P＜0.01).AG1478 组BBB 评分明显高于对照组(P＜0.01),且体重较对照组增加更明显(P＜0.05).结论:大鼠脊髓损伤后局部应用AG1478 治疗可明显改善损伤突触再生微环境,促进脊髓损伤神经功能的恢复.
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