Nogo受体拮抗剂对大鼠弥漫性轴索损伤神经保护作用及机制

Neuroprotective effects of Nogo receptor inhibitor on rat diffuse axonal injury model and mechanism

目的制作大鼠颅脑弥漫性轴索损伤模型，观察脑外伤后Nogo受体拮抗剂对大鼠脑外伤后的神经保护作用。方法自由落体硬膜外撞击方法制作大鼠颅脑弥漫性轴索损伤模型，分假手术组、对照组、实验组，伤后立即腹腔注射Nogo受体拮抗剂NEP1-40，伤后24h和72h神经行为学评分评价神经功能，酶联免疫吸附试验（ELISA）检测脑脊液中细胞因子白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的浓度，用Westernblot检测伤区脑组织中凋亡相关蛋白的表达水平。结果实验组的神经行为学评分（14．31±1．36）明显高于对照组（8．36±0．86），两组比较差异有统计学意义（P〈0．05）。实验组大鼠脑脊液中IL-1β和TNF-α的浓度较对照组明显下降，差异有统计学意义（P〈0．05）。实验组与对照比较，促凋亡蛋白bax表达下调，而抑制凋亡蛋白B淋巴细胞／白血病-2（bcl-2）表达上调。结论Nogo受体拮抗剂对大鼠脑外伤有明显的神经保护作用，其机制可能与阻断细胞因子的过度释放和抑制神经细胞的凋亡有关。

Objective Using a rat model of diffuse axonal injury to investigate the neruoprotecive effect of Nogo receptor inhibitor NEP1-40. Methods Free fall epidural hitting method was employed to establish an animal diffuse axonal injury model. NEP1-40 was intraperitoneally injected immediately after the injury. The nerve behavioral score was achieved at 24th and 72nd h after injury. Interleukin （IL） -115 and tumor necrosis factor （TNF）-a in cerebrospinal fl^id （CSF） were detected by using enzyme linked immunosorbent assay （ELISA）, and apoptosis relevant protein bax and B lymphocytes/leukemia-2 （bcl-2） expression was detected by using Western blotting. Results The nerve behavioral score in experimental group.[ （ 14. 31± 1.36） ] was significantly higher than in control group [ （8. 36 ±0. 86）, P 〈0. 05]. The IL-115 and TNF-cx levels in CSF of experimental group were signifieantly reduced as compared with control group （ P 〈 0. 05 ）. As compared with control group, the expression of bax was down-regulated, while that of bel-2 up-regulated in experimental group. Conclusion NEP1-40 has obvious neuro-protective effect against brain trauma of rats, probably by blocking excessive release of eytokines and suppressing apoptosis of neurons