胶质细胞源性神经营养因子缓释微球及NogoA,ChABC缓释微球联合应用损伤脊髓再生的形态学变化

背景：促进轴突再生的原则是改善抑制再生的环境和提高轴突生长能力,措施主要有轴突生长抑制因子阻滞剂和神经营养因子应用。用可降解微球加载药物是一种在局部提供持续药物释放的方法。目的：探讨胶质细胞源性神经营养因子、NogoA、ChABC缓释微球联合应用促进大鼠损伤脊髓再生病理形态学修复的作用。方法：建立SD大鼠T10脊髓完全横断伤模型,分别在损伤局部给予生理盐水、胶质细胞源性神经营养因子、胶质细胞源性神经营养因子缓释微球、NogoA缓释微球、ChABC缓释微球及3种微球联合治疗,并设立未造模的正常组及假手术组。损伤后10周,每组行四甲基若丹明葡聚糖胺顺行示踪,及神经丝蛋白200、生长相关蛋白43、胶质细胞源性神经营养因子免疫组化检查,并采用免疫组化图像分析系统进行定量分析。结果与结论：胶质细胞源性神经营养因子、NogoA、ChABC缓释微球联合能提高脊髓损伤局部神经丝蛋白200、生长相关蛋白43、胶质纤维酸性蛋白的表达水平,显示局部脊髓再生修复加强,其效果优于单用胶质细胞源性神经营养因子缓释微球。提示,胶质细胞源性神经营养因子缓释微球及NogoA,ChABC缓释微球联合促大鼠损伤脊髓再生修复其效果优于单用胶质细胞源性神经营养因子缓释微球。

Morphological changes of injured spinal cord following combined treatment of glial cell line-derived neurotrophic factor microspheres with NogoA and ChABC microspheres

BACKGROUND： The principle of promoting axonal regeneration is to improve the environment that inhibits axonal regeneration and to enhance the capacity of axonal growth, the main measures are the use of axonal growth inhibitory factor blockers and neurotrophic factors. Biodegradable microspheres loaded drugs is a method to provide local sustained release of drugs. OBJECTIVE： To evaluate the effect of glial cell line-derived neurotrophic factor （GDNF）, NogoA and ChABC microspheres on the regeneration and functional recovery of rats following spinal cord injury from a view of pathomorphological point. METHODS： Adult SD rats were used to establish spinal cord transective injury models, and were randomly divided into 8 groups： normal control group; sham operation group; local saline group; GDNF group; GDNF microspheres group; NogoA microspheres group; ChABC microspheres group; ChABC, GDNF and NogoA microspheres group. In normal control group and sham operation group, there was no model established. Ten weeks after injury, tetramethylrhodamine dextran amine anterograde neuronal tracing, immunohistochemistry and image analysis of neurofilament protein 200, GFAP and growth associated protein 43 were performed to assess the neurological regeneration. RESULTS AND CONCLUSION： ChABC, GDNF, NogoA microspheres can upgrade the expression of neurofilament protein 200, GFAP and growth associated protein 43 at spinal cord injury site, thus the regeneration and repair after spinal cord injury are obvious. ChABC, GDNF, NogoA microsphere is better than GDNF microspheres for the treatment of spinal cord injury. ChABC, GDNF, NogoA microspheres can promote the regeneration and repair of rats with transected spinal cord injury and is better than GDNF microspheres.