大鼠脊髓损伤后NGF及其受体TrkA在运动神经元及神经胶质细胞表达的变化

为探讨脊髓损伤后运动神经元及神经胶质细胞内神经生长因子(NGF)及其高亲和力受体(TrkA)表达的变化,用改良Allen重击法损伤SCI组动物T12脊髓,按伤后存活时间再将动物分为脊髓损1 d组、2 d组和5 d组。各组动物的脊髓切片经ABC法免疫组织化学染色,用光镜观察TrkA及NGF在脊髓前角运动神经元表达的变化和胶质纤维酸性蛋白(GFAP)及NGF免疫反应阳性胶质细胞的反应性增生程度,并进行图像分析。结果显示:脊髓损伤后前角运动神经元TrkA及NGF的表达随脊髓损伤后动物存活时间的延长逐渐上调;脊髓白质和灰质内尤其是皮质脊髓束内GFAP及NGF阳性胶质细胞明显增生;与此同时,室管膜细胞内亦可见明显的NGF免疫反应产物。上述结果表明,脊髓损伤可刺激脊髓前角运动神经元表达TrkA及NGF,通过自分泌维持受损神经元的存活;损伤部位反应性增生的胶质细胞亦可产生NGF,通过旁分泌作用于脊髓前角运动神经元或皮质脊髓束的轴突末梢,以维持运动神经元的存活及促进皮质脊髓束的再生;适时补充外源性神经营养素或改变损伤局部的微环境将有利于受损脊髓的修复和再生。

CHANGES OF NGF AND TrkA EXPRESSION IN THE MOTONEURONS AND GLIOCYTES FOLLOWING RAT SPINAL CORD INJURY

The present study was to explore the changes of NGF and TrkA expression in the motoneurons and gliocytes following spinal cord injury. Adult Sprague-Dawley rats were divided into three groups randomly; (1) Normal control group(n = 5); (2) Sham operation group(n=5); (3) SCI (spinal cord injury) group(n = 15) , and this group was further randomly subdivided into three subgroups according to the postoperative survival time, i. e. SCI 1 d group, SCI 2 d group and SCI 5 d group, . The animals of these subgroups suffered from weight-drop SCI operation on T12 spinal cord . The expression of TrkA and NGF in the motoneurons and NGF or GFAP irnmunoreactive positive gliocytes were examined by immunohistochemistry. After the SCI operation, the expression of NGF and TrkA in the motoneurons was gradually upregulated. The NGF positive gliocytes were different from GFAP positive gliocytes in morphology, and the two kinds of gliocytes were gradually increased after SCI operation. In addition, NGF expression in the ependyrnal cells was upregulated as well. Therefore, NGF and TrkA may play an important role in the intrinsic regeneration mechanisms of the injured spinal cord, and GFAP positive astrocytes may be one of inhibitors against neuronal regeneration due to the formation of glial scar. It is indicated that both application of neurotrophic factors and regulation of the microenvironment can promote regeneration of the injured spinal cord.