帕瑞昔布预先给药对大鼠局灶性脑缺血再灌注时水通道蛋白4表达的影响  

Effect of parecoxib pretreatment on expression of aquaporin-4 during focal cerebral ischemiaeperfusion in rats

作　　者：宋智敏[1] 周姝[2] 张春城[1] 潘振祥[1] 

机构地区：[1]吉林大学第二医院麻醉科,长春市130021 [2]吉林省肿瘤医院麻醉科

出　　处：《中华麻醉学杂志》2013年第5期630-632,共3页Chinese Journal of Anesthesiology

摘　　要：目的探讨帕瑞昔布预先给药大鼠局灶性脑缺血再灌注时水通道蛋白4（AQP4）表达的影响。方法成年雄性sD大鼠128只，6～8周龄，体重230～280g，采用随机数字表法，将其分为4组（n=32）：假手术组（s组）、缺血再灌注组（I／R组）、帕瑞昔布5mg／kg组（B组）和帕瑞昔布10mg／kg组（P10组）。采用线栓法阻塞大脑中动脉2h行再灌注的方法制备局灶性脑缺血再灌注损伤模型。R组和P10组分别于缺血前30rain经颈内静脉注射帕瑞昔布5、10mg／kg。分别于再灌注2、24h时行神经功能缺陷评分（NDS评分），然后处死大鼠，取脑，确定脑梗死体积，计算脑含水量；HE染色，光镜下观察病理学结果；并测定AQP4表达。结果与s组比较，其他3组NDS评分和脑含水量升高，脑梗死体积扩大，脑组织AQP4表达上调（P〈0．05或0．01）；与I／R组比较，B组和P10组NDS评分和脑含水量降低，脑梗死体积缩小，脑组织AQP4表达下调（P〈0．05或0．01）。光镜下P5组和P10组脑损伤程度明显轻于I／R组。结论帕瑞昔布预先给药减轻大鼠局灶性脑缺血再灌注损伤的机制与下调AQP4表达有关。Objective To investigate the effect of parecoxib pretreatment on the expression of aquaporin-4 （AQP4） during focal cerebral ischemia-reperfusion （I/R） in rats. Methods One hundred and twenty-eight adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 230-280 g, were randomly divided into 4 groups （ n = 32 each） ： sham operation group （S group）, I/R group, parecoxib 5 mg/kg group （group P5 ） and parecoxib 10 mg/kg group （group Plo ）. The rats were anesthetized with 10% chloral hydrate 3.5 ml/kg. Focal cerebral I/R was induced by 2 h middle cerebral artery occlusion followed by reperfusion. Parecoxib 5 and 10 mg/kg were injected via the right internal jugular vein at 30 min before middle cerebral artery occlusion in groups Ps and P^0, respectively. The equal volume of normal saline was injected instead of parecoxib in groups S and I/R. Neurological deficit score （NDS） was assessed at 2 and 24 h of reperfusion. The rats were then sacrificed and brains were removed for determination of infract volume （by TTC staining）. Brain water content was measured by wet/dry brain weight ratio. Their brains were cut into sections which were stained with haematoxylin and eosin and examined under microscope. The expression of AQP4 in brain tissues was measured. Results Compared with S group, NDS and brain water content were significantly increased, the infarct volume was enlarged, and the expression of AQP4 in brain tissues was up-regulated in I/R group （ P 〈 0.05 or 0.01 ）. NDS and brain water content were significantly lower, the infarct volume was smaller, and the expression of AQP4 in brain tissues was lower in groups P5 and P10 than in I/R group （P 〈 0.05 or 0.01 ）. Microscopic examination showed that brain injury was significantly attenuated in groups P5 and P10 as compared with I/R group. Conclusion The mechanism by which parecoxib pretreatment alle-viates the focal cerebral I/R injury in rats is related to down-regulation of the expression of AQP4.

关 键 词：环加氧酶抑制药 再灌注损伤 脑 水通道蛋白质4 

分 类 号：R285.5[医药卫生—中药学]