他克莫司对周围神经损伤后脊髓组织中肝细胞生长因子表达的影响

Effect of tacrolimus on expression of hepatocyte growth factor in rat spinal cord following peripheral nerve injury

[目的]探讨他克莫司对大鼠周围神经损伤后脊髓组织中肝细胞生长因子(HGF)表达的影响。[方法]成年雄性大鼠50只,随机分为正常组、损伤组和治疗组,后两组行双侧坐骨神经切断。术后治疗组颈后皮下注射他克莫司(1mg/kg),损伤组注射生理盐水。术后不同时间点取L4～6脊髓,应用Westernblotting技术及免疫荧光标记对脊髓组织中HGF的表达变化进行定量和定位检测。[结果]HGF在脊髓灰质前角、中间带和后角的各类神经元中均有表达;损伤组与正常组大鼠脊髓组织中HGF的表达之间无显著性差异(P>0.05),治疗组大鼠脊髓组织中HGF的表达在术后7、14d时明显高于损伤组(P<0.05)。[结论](1)周围神经损伤本身并不能使脊髓组织中HGF的表达上调;(2)他克莫司能诱导周围神经损伤后内源性HGF的高表达,从而保护相应神经元,促进轴突生长。

[ Objective] To explore the effect of tacrolimus on expression of hepatocyte growth factor （HGF） in rat spinal cord following peripheral nerve injury. [ Method] Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by transection of bilateral sciatic nerve at 0.5 cm distal to piriform muscle. Then treatment group received subcutaneous injection of tacrolimus （ 1 mg/kg） at the back of the neck,while injury group received 0.9 % saline. The L4-6 spinal cords were harvested at various time points after surgery. Western blotting and immunofluorescence staining were used to detect the level and position of HGF in the spinal cord. [ Result]HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. There was no significant difference in the expressions of HGF between injury group and normal group, while the expression of HGF was significantly higher in treatment group than that in injury group at 7 and 14 days after surgery. [ Conclusion] Peripheral nerve injury does not up-regulate the expression of HGF in spinal cord, while tacrolimus can induce high expression of endogenous HGF after injury to protect neurons and promote axonal outgrowth.