Ozturk Bilgin Ozlem, Kumbul Doguc Duygu, Altuntas Irfan, Sutcu Recep, Delibas Namık
Konak Hospital, Medical Biochemistry Department, Izmit, Turkey.
Suleyman Demirel University, Medical Faculty, Medical Biochemistry Department, Isparta, Turkey.
Iran J Pharm Res. 2013 Fall;12(4):877-85.
Several studies point to an important function of cyclooxygenase (COX) and prostaglandin signaling in models of synaptic plasticity which is associated with N-methyl-D-aspartate receptors (NMDARs). Cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by NMDA dependent synaptic activity. Nonsteroid Antiinflammatory Drugs (NSAIDs) exert their antiinflammatory effect by the inhibion of COX have controversial effects on learning and memory. We administered ibuprofen as a non-selective COX-2 inhibitor and nimesulide as a selective COX-2 inhibitor for 8 weeks for determining the cognitive impact of subchronic administration of NSAIDs to aged rats. Wistar albino rats (16 mo, n = 30) were separated into control (n = 10), ibuprofen (n = 10) and nimesulide (n = 10) treated groups. First we evaluated hippocampus-dependent spatial memory in the radial arm maze (RAM) and than we evaluated the expression of the NMDAR subunits, NR2A and NR2B by western blotting to see if their expressions are effected by subchronic administration with these drugs. Ibuprofen and nimesulide treated rats completed the task in a statistically significant shorter time when compared with control group (p < 0.01), but there was no statistically significant difference between groups about choice accuracy data in RAM. Furthermore, no statistically significant difference was detected for the protein expressions of NR2A and NR2B of the subjects. Oral administration of ibuprofen and nimesulide for 8 weeks showed no impairment but partly improved spatial memory.
多项研究指出，环氧化酶（COX）和前列腺素信号传导在与N-甲基-D-天冬氨酸受体（NMDARs）相关的突触可塑性模型中具有重要作用。环氧化酶基因被认为是一种即时早期基因，在神经元中受到NMDA依赖性突触活动的严格调控。非甾体抗炎药（NSAIDs）通过抑制COX发挥抗炎作用，但其对学习和记忆的影响存在争议。我们给予布洛芬作为非选择性COX-2抑制剂，尼美舒利作为选择性COX-2抑制剂，持续8周，以确定NSAIDs亚慢性给药对老年大鼠认知的影响。将Wistar白化大鼠（16个月，n = 30）分为对照组（n = 10）、布洛芬治疗组（n = 10）和尼美舒利治疗组（n = 10）。首先，我们在放射状臂迷宫（RAM）中评估海马依赖性空间记忆，然后通过蛋白质印迹法评估NMDAR亚基NR2A和NR2B的表达，以观察这些药物的亚慢性给药是否会影响它们的表达。与对照组相比，布洛芬和尼美舒利治疗的大鼠完成任务的时间在统计学上显著缩短（p < 0.01），但在RAM中的选择准确性数据方面，各组之间没有统计学上的显著差异。此外，未检测到受试者NR2A和NR2B蛋白表达的统计学显著差异。口服布洛芬和尼美舒利8周未显示出损害，反而部分改善了空间记忆。
