Resnick D K, Graham S H, Dixon C E, Marion D W
Department of Neurological Surgery, University of Wisconsin Medical School, Madison 53792, USA.
J Neurotrauma. 1998 Dec;15(12):1005-13. doi: 10.1089/neu.1998.15.1005.
Cyclooxygenase, or prostaglandin G/H synthase, is the rate-limiting step in the production of prostaglandins. A new isoform, cyclooxygenase-2 (COX-2), has been cloned that is induced during inflammation in leukocytes and by synaptic activity in neurons. The objectives of this study are to determine the nature of COX-2 expression in normal and traumatized rat spinal cord, and to determine the effects of selective COX-2 inhibition on functional recovery following spinal cord injury. Using a weight-drop model of spinal cord injury, COX-2 mRNA expression was studied with in situ hybridization. COX-2 protein expression was examined by immunohistochemistry and Western analysis. Finally, using the highly selective COX-2 inhibitor, 1-[(4-methylsufonyl)phenyl]-3-tri-fluro-methyl-5-[(4-flur o)phenyl]prazole (SC58125), the effect of COX-2 inhibition on functional outcome following a spinal cord injury was determined. COX-2 was expressed in the normal adult rat spinal cord. COX-2 mRNA and protein production were increased following injury with increases in COX-2 mRNA production detectable at 2 h following injury. Increased levels of COX-2 protein were detectable for at least 48 h following traumatic spinal cord injury. Selective inhibition of COX-2 activity with SC58125 resulted in improved mean Basso, Beattie, and Bresnahan scores in animals with 12.5- and 25-g/cm spinal cord injuries; however, the effect was significant only for the 12.5g/cm injury group (p=0.0001 vs. p=0.0643 in the 25-g/cm group). These data demonstrate that COX-2 mRNA and protein expression are induced by spinal cord injury, and that selective inhibition of COX-2 improves functional outcome following experimental spinal cord injury.
环氧化酶，即前列腺素G/H合酶，是前列腺素生成过程中的限速步骤。一种新的同工型，环氧化酶-2（COX-2），已被克隆出来，它在白细胞炎症期间以及神经元的突触活动中被诱导产生。本研究的目的是确定正常和创伤大鼠脊髓中COX-2表达的性质，并确定选择性抑制COX-2对脊髓损伤后功能恢复的影响。使用脊髓损伤的重物坠落模型，通过原位杂交研究COX-2 mRNA表达。通过免疫组织化学和蛋白质印迹分析检测COX-2蛋白表达。最后，使用高度选择性的COX-2抑制剂1-[(4-甲基磺酰基)phenyl]-3-三氟甲基-5-[(4-氟)phenyl]吡唑（SC58125），确定抑制COX-2对脊髓损伤后功能结局的影响。COX-2在正常成年大鼠脊髓中表达。损伤后COX-2 mRNA和蛋白产生增加，损伤后2小时即可检测到COX-2 mRNA产生增加。创伤性脊髓损伤后至少48小时可检测到COX-2蛋白水平升高。用SC58125选择性抑制COX-2活性可使脊髓损伤为12.5 g/cm和25 g/cm的动物的平均Basso、Beattie和Bresnahan评分提高；然而，该效应仅在12.5 g/cm损伤组中显著（25 g/cm组中p = 0.0643，与之相比，12.5 g/cm组中p = 0.0001）。这些数据表明，脊髓损伤可诱导COX-2 mRNA和蛋白表达，并且选择性抑制COX-2可改善实验性脊髓损伤后的功能结局。
