Taoka Y, Okajima K, Murakami K, Johno M, Naruo M
Department of Laboratory Medicine, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto 860, Japan.
Brain Res. 1998 Jul 20;799(2):264-9. doi: 10.1016/s0006-8993(98)00459-4.
We have previously demonstrated the importance of activated neutrophils in compression-induced spinal cord injury (SCI) in rats. In the present study, we investigate the action of neutrophil elastase in posttraumatic SCI, using two neutrophil elastase inhibitors (Eglin C and L658,758). SCI was induced by applying a 20-g weight to the spinal cord for 20 min at the level of T12, resulting in hindlimbs motor disturbances, which, when evaluated using a inclined-plane test, were significantly attenuated by Eglin C or L658,758. Histologic examination revealed that intramedullary hemorrhages observed 24 h after trauma were markedly attenuated in these agents. These inhibitors also significantly decreased neutrophil accumulation as shown by myeloperoxidase activity in the damaged spinal cord segment. Induction of leukocytopenia had the same effects as Eglin C or L658,758. These findings implicated neutrophil elastase in SCI. The enzyme may induce vascular damage leading to spinal cord ischemia.
我们之前已经证明了活化的中性粒细胞在大鼠压迫性脊髓损伤(SCI)中的重要性。在本研究中,我们使用两种中性粒细胞弹性蛋白酶抑制剂(埃格林C和L658,758)来研究中性粒细胞弹性蛋白酶在创伤后脊髓损伤中的作用。通过在T12水平对脊髓施加20克重物20分钟来诱导脊髓损伤,导致后肢运动障碍,使用斜面试验评估时,埃格林C或L658,758可显著减轻这种障碍。组织学检查显示,创伤后24小时观察到的髓内出血在这些药物作用下明显减轻。这些抑制剂还显著减少了中性粒细胞的积聚,受损脊髓节段中的髓过氧化物酶活性表明了这一点。诱导白细胞减少具有与埃格林C或L658,758相同的效果。这些发现表明中性粒细胞弹性蛋白酶与脊髓损伤有关。该酶可能会导致血管损伤,进而导致脊髓缺血。