Effect Of Parecoxib Pretreatment On Focal Cerebral Ischemia-Reperfusion Injury In Rats

Objective: To investigate the effect of parecoxib pretreatment on focal cerebral ischemia-reperfusion injury in rats and the mechanism involved.Methods: Sixty-four male SD rats weighing 250-300g were randomly divided into 4 groups(n=16): sham operation group (group S); focal cerebral I/R group (group I/R); focal cerebral I/R+ parecoxib 5 mg/kg(group P5);focal cerebral I/R group (group I/R); focal cerebral I/R+ parecoxib 10 mg/kg(group P10).Focal cerebral I/R was produced by occlusion of middle cerebral artery for two hours followed by 24h of reperfusion . Parecoxib 5mg/kg and 10mg/kg were injected intravenously through the internal jugular vein 30minutes before ischemia in P5 group and P10 group respectively. The neurologic deficit scores(NDS) were measured at 24 hours of reperfusion and then the rats were decapitated. Brains were rapidly removed for determination of the infarct volume, apoptotic index, and expression of Bcl-2,Bax,GFAP,the content of PGE2,IL-1βand TNF-αin rats brain. The ratio of Bcl-2 and Bax was calculated(Bcl-2/ Bax). Results: The NDS,apoptotic rate,expression of Bcl-2,Bax,GFAP ,and the content of PGE2,IL-1β,TNF-αin brain were significantly higher in I/R group than in group S(P<0.01). The 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 NDS was significantly lower in group P10, the apoptosis rate,Bax,GFAP,PGE2,IL-1β,TNF-αwere significantly lower, the infarct volume were significantly smaller, Bcl-2 expression and Bcl-2/Bax were significantly higher in group P5 and P10 than in I/R group(P<0.05 or 0.01).The infarct volume was significantly smaller, the apoptosis rate and Bax,GFAP expression and the content of PGE2,IL-1β,TNF-αin brain were significantly lower,and Bcl-2 expression and Bcl-2/Bax were significantly higher in group P10 than in group P5(P<0.05or 0.01).Pretreatment with parecoxib 5mg/kg or 10mg/kg significantly reduced histopathological injury in CA1 region of hippocampus . Moreover the effect of reducing histopathological injury in CA1 region of hippocampus in group P10 is better than group P5.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 experssion and down-regulation of Bax expression; reduce PGE2 levels in brain tissue, Inhibition of excessive activation of astrocytes, down-regulation the GFAP.Reduce the release of IL-1β,TNF-αin rats.