Role of cyclooxygenase 2 in acute spinal cord injury.
Role of cyclooxygenase 2 in acute spinal cord injury.
复制标题
环氧合酶2在急性脊髓损伤中的作用。
DOI：
10.1089/neu.1998.15.1005
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Marion,DW
中科院分区：
文献类型：
--
作者：
Resnick,DK;Graham,SH;Dixon,CE;Marion,DW
环加氧酶或前列腺素G/H合酶是前列腺素生产中的限速步骤。一种新的同工型，环氧合酶-2（考克斯-2），已被克隆，它在白细胞炎症过程中和神经元突触活动中被诱导。本研究的目的是确定考克斯-2在正常和创伤大鼠脊髓中表达的性质，并确定选择性考克斯-2抑制对脊髓损伤后功能恢复的影响。应用原位杂交技术研究脊髓损伤后考克斯-2 mRNA的表达。免疫组化和Western分析检测考克斯-2蛋白的表达。最后，使用高度选择性的考克斯-2抑制剂1-[（4-甲基磺酰基）苯基]-3-三氟-甲基-5-[（4-氟）苯基]吡唑（SC 58125），确定考克斯-2抑制对脊髓损伤后功能结果的影响。考克斯-2在正常成年大鼠脊髓中表达。损伤后考克斯-2 mRNA和蛋白质的产生增加，损伤后2 h可检测到考克斯-2 mRNA的产生增加。在创伤性脊髓损伤后至少48 h可检测到考克斯-2蛋白水平升高。用SC 58125选择性抑制考克斯-2活性可改善12.5 g/cm和25 g/cm脊髓损伤动物的平均Basso、Beattie和Bresnahan评分;然而，仅对12.5 g/cm损伤组有显著影响（p= 0.0001 vs. 25 g/cm组p= 0.0643）。这些数据表明，考克斯-2 mRNA和蛋白质的表达是由脊髓损伤诱导的，并且选择性抑制考克斯-2改善了实验性脊髓损伤后的功能结果。
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 within situhybridization. COX-2 protein expression was examined by immunohistochemistry and Western analysis. Finally, using the highly selective COX-2 inhibitor, l-[(4-methylsufonyl)phenyl]-3-trifluro-methyl-5-[(4-fluro)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 12.5-g/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.