Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.
Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.
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发表时间：
2011-07
影响因子：
6.1
通讯作者：
Na Wang;Q. Guo;Z. Ye;Ping-ping Xia;E. Wang;Ya-jing Yuan
中科院分区：
文献类型：
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作者：
Na Wang;Q. Guo;Z. Ye;Ping-ping Xia;E. Wang;Ya-jing Yuan
研究背景环氧化酶-2（考克斯-2）参与缺血性脑损伤的延迟进展。本研究旨在研究帕瑞昔布抑制考克斯-2是否能减轻大鼠局灶性脑缺血/再灌注损伤。方法雄性SD大鼠90只，随机分为假手术组、缺血再灌注（I/R）组和帕瑞昔布组。帕瑞昔布组于缺血前15 min经阴茎背静脉注射帕瑞昔布4 mg/kg，缺血后12 h再次注射帕瑞昔布4 mg/kg。分别于再灌注后24和72 h进行神经功能缺损评分（NDS）。然后对大鼠实施安乐死。取脑进行苏木精-伊红染色、尼氏染色，并测定高迁移率族蛋白1（HMGB 1）和肿瘤坏死因子-α（TNF-α）水平。用2，3，5-氯化三苯基四唑（TTC）染色评估脑体积。结果与假手术组比较，I/R组大鼠NDS降低（P < 0.05），梗死体积增大（P < 0.05），HMGB 1水平降低（P < 0.05），TNF-α水平升高（P < 0.05）。帕瑞昔布治疗组NDS明显改善，梗死体积缩小，HMGB 1和TNF-α水平降低（P < 0.05）。结论：静脉注射帕瑞昔布预处理具有神经保护作用。其作用可能与减轻炎症反应和抑制炎症介质有关。
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.