Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Chin Med J (Engl). 2011 Jul 5;124(13):2004-8.
Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.
Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.
The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05).
Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.
多项研究表明环氧化酶-2（COX-2）有助于延迟缺血性脑损伤的进展。本研究旨在探讨 COX-2 抑制剂帕瑞昔布是否能减轻大鼠局灶性脑缺血再灌注损伤。
90 只雄性 Sprague-Dawley 大鼠随机分为三组：假手术组、缺血再灌注（I/R）组和帕瑞昔布组。帕瑞昔布组在缺血前 15 分钟通过阴茎背静脉给予 4mg/kg 帕瑞昔布，再灌注后 12 小时再次给予。在再灌注后 24 小时和 72 小时评估神经功能缺损评分（NDS）。然后处死大鼠。取出大脑进行苏木精-伊红染色、尼氏染色以及高迁移率族蛋白 B1（HMGB1）和肿瘤坏死因子-α（TNF-α）水平的测量。用 2,3,5-三苯基四氮唑氯化物（TTC）染色评估梗死体积。
与假手术组相比，I/R 组大鼠的 NDS 评分较低（P < 0.05），梗死体积较大（P < 0.05），HMGB1 水平较低（P < 0.05），TNF-α水平较高（P < 0.05）。帕瑞昔布给药显著改善了 NDS，减小了梗死体积，降低了 HMGB1 和 TNF-α水平（P < 0.05）。
静脉内给予帕瑞昔布预处理具有神经保护作用。其作用可能与抑制炎症反应和炎症介质有关。
