Transient global cerebral ischemia (tGCI) induces inflammation leading to secondary brain injury. Data suggested that cyclooxygenase-2 (COX-2) is involved in the occurrence and development of inflammatory reaction after reperfusion; however, the effectiveness of a highly selective COX-2 inhibitor, parecoxib, to counteract tGCI remains to be determined. Thus, the aim of this study was to investigate the potential protective actions of parecoxib in a rat model of tGCI and the role inflammation plays in this disorder. Adult male Sprague-Dawley rats were administered parecoxib 10 or 20 mg/kg intraperitoneally (ip) at 5 min, 24 or 48 hr after tGCI. Control rats received an equal volume of 0.9% saline. The rat model of tGCI was established using the method of bilateral common carotid artery occlusion combined with arterial hypotension. The following parameters were measured: Neurological Severity Score, morphological changes in the hippocampal CA1 region, Evans blue (EB) extravasation, brain water content, levels of matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), neuronal apoptosis, the protein expression of Bcl-2, Bax, COX-2, prostaglandin E2 (PGE₂), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Parecoxib treatment significantly improved neurological function and morphological defects in the hippocampal CA1 region, reduced levels of COX-2, PGE₂, IL-1β, and TNF-α. In addition, parecoxib attenuated brain edema and BBB destruction as evidenced by increased ZO-1 expression and decreased MMP-9 expression. Further, parecoxib reduced neuronal apoptosis via diminished protein expression of Bax and enhanced expression of Bcl-2.

短暂性全脑缺血（tGCI）引起炎症，导致继发性脑损伤。数据表明，环氧合酶2（COX-2）参与了再灌注后炎症反应的发生和发展。然而，高选择性COX-2抑制剂帕瑞昔布（parecoxib）对抗tGCI的有效性仍有待确定。因此，本研究的目的是研究帕瑞昔布在tGCI大鼠模型中的潜在保护作用以及炎症在该疾病中的作用。成年雄性Sprague-Dawley大鼠在tGCI后5分钟，24或48小时腹膜内（ip）施用parecoxib 10或20 mg / kg。对照大鼠接受等体积的0.9％盐水。采用双侧颈总动脉闭塞结合动脉低血压的方法建立了tGCI大鼠模型。CA1区，伊文思蓝（EB）外渗，脑水含量，基质金属蛋白酶9（MMP-9）水平，小支闭合带1（ZO-1），神经元凋亡，Bcl-2，Bax，COX的蛋白表达-2，前列腺素E2（PGE ₂），白介素1β（IL -1β ）和肿瘤坏死因子-α（TNF -α ）。帕瑞昔布治疗可显着改善海马CA1区的神经功能和形态缺陷，降低COX-2，PGE ₂，IL - 1β和TNF的水平-α。此外，帕瑞昔布可减轻脑水肿和BBB破坏，这可通过增加ZO-1表达和降低MMP-9表达来证明。此外，帕瑞昔布通过减少Bax蛋白表达和增强Bcl-2表达来减少神经元凋亡。