帕瑞昔布钠预先给药对大鼠局灶性脑缺血再灌注损伤的影响

Effect of parecoxib pretreatment on focal cerebral ischemia-reperfusion injury in rats

目的 评价帕瑞昔布钠预先给药对大鼠局灶性脑缺血再灌注损伤的影响.方法 雄性SD大鼠64只,体重250～300 g,随机分为4组（n=16）：假手术组（S组）、缺血再灌注组（I/R组）、缺血再灌注＋帕瑞昔布钠5 mg/kg组（P5组）和缺血再灌注＋帕瑞昔布钠10 mg/kg组（P10组）.I/R组、P5组和P10组采用线栓法进行脑缺血2 h.P5组和P10组在缺血前30 min时分别经颈内静脉注射帕瑞昔布钠5、10 mg/kg.再灌注24 h时进行神经功能缺陷评分,然后取脑组织,测定脑梗死体积、细胞凋亡率、Bc1-2和Bax表达,并计算Bcl-2与Bax的比值（Bcl-2/Bax）.结果 与S组比较,I/R组神经功能缺陷评分、细胞凋亡率、Bcl-2及Bax表达均升高,Bcl-2/Bax降低,脑梗死体积增大（P＜0.01）.与I/R组比较,P10组神经功能缺陷评分降低,P5组和P10组细胞凋亡率和Bax表达降低,脑梗死体积缩小,Bcl-2表达和Bcl-2/Bax升高（P＜0.05或0.01）.与P5组比较,P10组脑梗死体积缩小,细胞凋亡率和Bax表达降低,Bcl-2表达和Bcl-2/Bax升高（P＜0.05或0.01）.结论 帕瑞昔布钠预先给药可减轻大鼠局灶性脑缺血再灌注损伤,且与剂量有关,其机制与上调Bcl-2表达、下调Bax表达从而抑制细胞凋亡有关.

Objective To investigate the effect of parecoxib pretreatment on focal cerebral ischemia-reperfusion （I/R） injury in rats. Methods Sixty-four male SD rats weighing 250-300 g were randomly divided into 4 groups （ n= 16 each）： sham operation group （group S）; focal cerebral I/R group; focal cerebral I/R ＋ parecoxib 5 mg/kg group （group P5）; focal cerebral I/R ＋ parecoxib 10 mg/kg group （group P10）. Focal cerebral I/R was produced by occlusion of middle cerebral artery for 2 h followed by 24 h of reperfusion. Parecoxib 5 and 10 mg/kg were injected intravenously through the internal jugular vein 30 min before ischemia in group P5 and P10 respectively. The neurologic deficit scores （NDSs） were measured at 24 h of reperfusion and then the rats were decapitated.Brains were rapidly removed for determination of the infarct volume, apoptosis rate and expression of Bcl-2 and Bax. The ratio of Bcl-2 to Bax （Bcl-2/Bax） was calculated. Results The NDSs, apoptosis rate and expression of Bcl-2 and Bax were significantly higher, Bcl-2/Bax was significantly lower, and the infarct volume was significantly larger in group I/R than in group S （ P ＜ 0.01 ）. The NDSs were significantly lower in group P10, and the apoptosis rate and Bax expression were significantly lower, the infarct volume was significantly smaller, Bcl-2 expression and Bcl-2/Bax were significantly higher in group P5 and P10 than in group I/R （P ＜0.05 or 0.01）. The infarct volume was significantly smaller, the apoptosis rate and Bax expression were significantly lower, and Bcl-2 expression and Bcl-2/Bax were significantly higher in group P10 than in group P5 （ P ＜ 0.05 or 0.01 ）. Conclusion Pretreatment with parecoxib can attenuate focal cerebral I/R injury in a dose-dependent manner through inhibition of cell apoptosis via up-regulation of Bcl-2 expression and down-regulation of Bax expression in rats.