不同浓度帕瑞昔布钠预处理对大鼠局灶性脑缺血－再灌注损伤保护作用的研究

摘要

Objective To investigate the protective effects of different concentration of parecoxib pretreatment on focal cere -bral ischemia-reperfusion(I/R)injury in rats.Methods One hundred and twenty eight male SD rats were randomly divided into sham operation group(group S),simple focal cerebral I /R group(group I /R) and six focal cerebral I /R+parecoxib pretreatment groups (group P1,P2,P3,P4 P5 and P6).Total were 8 groups,16 animals in each group.Rat middle cerebral artery ischemia model (MCAO) was set-up by using a suture-occluded method.Reperfusion was performed for 24 hours after 2 hour of ischemia.2,4,6,8,10,20 mg/kg of parecoxib were injected via inter jugular vein 30 min before ischemia in the groups P1 ~P6 while equal volume of saline was given in the group S and the group I /R.The neurological deficit scores (NDSs)were measured at 2 h after ischemia and at the end of 24 hours of reperfusion.The infarct volume and volume percentage were measured using TTC staining .Prostaglandin E2(PGE2 )content in the ische-mic frontal cortex was measured using a radioimmunoassay .Results The NDSs,the volume of cerebral infarcts and the percentage of cerebral infarcts,and the PGE2 content in the groups P1 ~P6 were significantly higher than that in the group S but lower than that in the group I/R(all P <0.05).These indexes were gradually decreased with the increasing doses of parecoxib when the group P 1 to p6 were compared(all P <0.05).Conclusion Pretreatment with parecoxib has protective effect on focal cerebral I /R injury in rats and it has strongest effect at 20 mg/kg.%目的：探讨不同浓度帕瑞昔布钠预处理对大鼠局灶性脑缺血－再灌注损伤的保护作用。方法雄性 SD 大鼠128只，采用随机数字表法分为假手术组（S 组）、单纯缺血再灌注组（I／R 组）、缺血再灌注＋帕瑞昔布预处理组（P1、P2、P3、P4、P5、P6组）共8组，每组16只大鼠。线栓法制作大鼠大脑中动脉缺血模型（MCAO），缺血后2 h 后再灌注24 h。在缺血前30 min，P1～P6组分别经颈内静脉注入2、4、6、8、10、20 mg／kg 帕瑞昔布钠；S 组和 I／R 组分别注入等容积生理盐水。比较各组缺血2 h 及再灌注24 h 行神经功能缺失评分、脑梗死体积及体积百分比、缺血侧额区皮质中前列腺素 E2（PGE2）含量。结果P1～P6组神经功能缺失评分、缺血再灌注后脑梗死体积、梗死体积百分比及 PGE2含量均高于 S 组，但低于 I／R 组，差异均有统计学意义（P ＜0．05）。随帕瑞昔布钠浓度升高，P1～P6组神经功能缺陷评分、脑梗死体积、脑梗死体积百分比及缺血侧额区皮质 PGE2含量均逐渐降低，差异有统计学意义（均 P ＜0．05）。结论帕瑞昔布预处理对大鼠局灶性脑缺血再灌注损伤具有保护作用，20 mg／kg 保护作用最强。