抑制一氧化氮合酶活性促进大鼠脊髓损伤修复

INHIBITION OF NITRIC OXIDE SYNTHASE IMPROVES REPAIR OF SPINAL CORD INJURY IN THE RAT

NO是兼有细胞间第二信使和细胞毒性作用的气体性神经活性物质。过量NO是导致神经细胞死亡的主要因素之一、应用大鼠脊髓磁控过半夹损模型，在施加NOS抑制剂L－NAME和生理盐水作为对照条件下，手术后8周内动态观察行为学、电生理学和形态学变化．结果表明；损伤后1周，后肢行为能力逐渐增强，其中抑制剂组恢复速度较快、程度也较好，可记录到恢复的下行性脊髓诱发电位，在空洞形成和脊髓萎缩程度方面抑制剂组也均明显轻于对照组，抑制剂组未见NOS表达；但对照组伤后NOS阳性神经元渐增，至4周时达较高水平．后渐降并伴有损伤区不断扩大，神经元尼氏体移位、减少或消失。结果提示；神经损伤可诱导NOS表达，NOS抑制剂L－NAME对脊髓损伤的修复有促进作用，其机制可能与NO介导的神经毒性受阻有关。

Nitric oxide (No) is a gaseous neural active substance acting as both second rnessenger and cellular toxicant. Ex-cessive NO is one of the major factors leading to neuronal death. The present study aimed at dynamically observing the be-havioral, electrophysiological and histological changes induced by spinal cord injury (SCI) and the effect of NO synthase (NOS) inhibitor, N-Nitro-L-Arginine Methyl Ester (L-NAME), on the repairation of the injury during 8 weeks. one week after injury, behavioral abilities of the rats;hindlimbs recovered gradually. In grorp L-NAME, the hindrance of hindlimbs was lighter and the recovery was more rapid and better than those in group NS l descending spinal field potential were recov-ered and recorded in group L-NAME. Morphologically, the degree of cavity formation and SC atrophy in group NS was markedly more serious than those in group L-NAME;and the number of NOS-positive neurons was increased gradually after SCI and reached a higher level in about 4 weeks and then was decreased but the Iesion area enlarged; Nissl body in SC neu-rons became translocated, decreased in amount or vanished, whereas all these changes were much le8s in group L-NAME.These rsults indicate that CNS injury induces the expression of NOS, the NOS inhibitor L-NAME improves the repair of SCI, and its mechanism seems to be related to the bIockade of NO's neurotoxicity.