Naruo Seiichiro, Okajima Kenji, Taoka Yuji, Uchiba Mitsuhiro, Nakamura Takafumi, Okabe Hiroaki, Takagi Katsumasa
Department of Orthopedic Surgery, Kumamoto University School of Medicine, Kumamoto, Japan.
J Neurotrauma. 2003 Feb;20(2):221-8. doi: 10.1089/08977150360547125.
Prostaglandin E1 (PGE1), a potent vasodilator, was recently reported to inhibit both neutrophil activation and monocytic production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We previously reported that TNF-alpha was critically involved in the development of motor disturbances by increasing the accumulation of neutrophils at the site of injury in rats subjected to compression trauma-induced spinal cord injury. Therefore, it is possible that PGE1 reduces motor disturbances by inhibiting neutrophil activation in rats subjected to spinal cord injury. We examined this possibility in a rat model of spinal cord injury (SCI). Motor disturbances induced by spinal cord compression were evaluated using the inclined plane test, and footprint analysis. Accumulation of neutrophils at the site of trauma was evaluated by measuring tissue myeloperoxydase (MPO) activity. Tissue levels of TNF-alpha were determined using an enzyme-linked immunosorbent assay. Motor disturbances induced by spinal cord compression were significantly attenuated in rats administered PGE1. A histological examination revealed that intramedullary hemorrhages, observed 24 h after trauma, were markedly reduced in animals administered PGE1. Increases in the tissue levels of TNF-alpha and MPO activity in the damaged segment of spinal cord were significantly inhibited in animals that had received PGE1. These observations suggested that PGE1 reduces motor disturbances by inhibiting neutrophil activation directly or indirectly through the inhibition of TNF-alpha production at the site of injury. These effects of PGE1 might at least partly contribute to therapeutic effect on SCI in rats.
前列腺素E1（PGE1）是一种强效血管扩张剂，最近有报道称其在体外可抑制中性粒细胞活化以及单核细胞产生肿瘤坏死因子-α（TNF-α）。我们之前报道过，在遭受压迫性创伤诱导的脊髓损伤的大鼠中，TNF-α通过增加损伤部位中性粒细胞的聚集，在运动障碍的发生发展中起关键作用。因此，PGE1有可能通过抑制脊髓损伤大鼠的中性粒细胞活化来减轻运动障碍。我们在大鼠脊髓损伤（SCI）模型中检验了这种可能性。使用斜面试验和足迹分析评估脊髓压迫诱导的运动障碍。通过测量组织髓过氧化物酶（MPO）活性来评估创伤部位中性粒细胞的聚集情况。使用酶联免疫吸附测定法测定组织中TNF-α的水平。给予PGE1的大鼠中，脊髓压迫诱导的运动障碍明显减轻。组织学检查显示，创伤后24小时观察到的髓内出血在给予PGE1的动物中明显减少。在接受PGE1的动物中，脊髓损伤节段组织中TNF-α水平和MPO活性的升高受到显著抑制。这些观察结果表明，PGE1通过直接或间接抑制损伤部位TNF-α的产生来抑制中性粒细胞活化，从而减轻运动障碍。PGE1的这些作用可能至少部分有助于对大鼠SCI的治疗效果。
