Nogo受体拮抗剂对大鼠急性脊髓损伤保护作用.docVIP

Nogo受体拮抗剂对大鼠急性脊髓损伤保护作用 　 作者：吴继彬，杨惠林，张钦，邱志杰，丁涛 【摘要】 目的 探讨Nogo受体拮抗剂NEP1-40对大鼠脊髓损伤后脊髓功能恢复的影响，为临床治疗急性脊髓损伤提供实验依据。方法 健康Wistar大鼠48只随机分为创伤对照组、NEP1-40治疗组。建立大鼠中段胸部脊髓后半部横切模型。对照组注入生理盐水，实验组采用NEP1-40治疗。分别在术后取材行苏木精-伊红染色、免疫荧光染色检测。术后第1、3天及1、2、3、4周对动物进行运动功能评分。结果 脊髓损伤3周后，NEP1-40组行为学评分高于对照组，同时NeuN/NF-200阳性染色亦明显高于对照组，差异有统计学意义。结论 NEP1-40治疗脊髓损伤能促进神经元的再生，恢复脊髓功能。 【关键词】 大鼠；脊髓损伤；Nogo受体拮抗剂；再生 　　Abstract: Objective To investigate the effects of Nogo receptor antagonist (NEP1-40) on the rehabilitation of spinal cord following spinal cord injury (SCI) in adult rats model, and provide experimental bases for clinical treatment of acute SCI. Methods 48 healthy Wistar rats were randomized into two groups: the trauma control group and the experimental group (NEP1-40 group). Rat model of middle thoracic spinal cord post half transsection was established. The experimental group was treated with NEP1-40 and the control group was treated with saline injection following SCI. Postoperatively, samples collected from each group underwent detections by HE staining and an immunofluorescence staining. Rat behavior function was evaluated at such time points as the post-injury 1 and 3 days, 1, 2, 3 and 4 weeks. Results 3 weeks after SCI, the BBB score was higher in NEP1-40 group than that in the trauma control group. The positive immunofluorescence area of NeuN/NF-200 in NEP1-40 group was also larger than that in the control group. Quantitative analysis showed that these differences had statistical significance. Conclusion NEP1-40 in the treatment of SCI is able to promote nerve axon regeneration of injured sites and rehablitate spinal electrophysiological and motor functions. 　　Key words: rats; spinal cord injury; Nogo receptor antagonist; regeneration 脊髓少突胶质细胞所分泌的Nogo蛋白是目前已知最强的神经轴突生长抑制因子，对受损神经元再生具有极强的抑制作用［1］。Nogo受体拮抗剂(Nogo extracellular peptide, residues 1-40，NEP1-40)为针对Nogo-66氨基序列设计的Nogo受体(Nogo receptor，NgR)竞争性拮抗剂，能拮抗中枢神经抑制因子与NgR的结合，起到促进神经再生的作用［1-2］。本实验主要观察NEP1-40对于急性脊髓损伤大鼠运动功能的影响及对NF-200表达的影响，并进一步探讨NEP1-4