Effects of flurbiprofen pretreatment on global cerebral ischemia-reperfusion injury in rats

Objective To investigate the effects of pretreatment with flurbiprofen on global cerebral ischemia-repeffasion (IR) injury in rats and the mechanism involved. Methods Eighty-four male SD rats weighing 200-350 g were randomly divided into 4 groups (n = 21 each): group Ⅰ sham operation (group S); group Ⅱ global cerebral IR (group IR); group Ⅲ flurbiprofen 5 mg/kg + global cerebral IR (group F_1) and group Ⅳ flurbiprofen 10 mg/kg + global cerebral IR (group F_2). Global cerebral ischemia was induced by 20 rain occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mm Hg). In group F_1 and F_2 flnrbiprofen 5 and 10 mg/kg was injected iv at 15 min before ischemia respectively. The neurological deficit score (NDS) was assessed (0=normal, 100 = brain death) at 6 h (T_1), 24 h (T_2) and 72 h (T_3) of reperfusion by the same observer. Blood samples were taken from left internal jugular vein. And then the animals were killed and brains removed for determination of serum concentrations of TNF-α and IL-1β(using radioimmunoassay), expression of nuclear factor-kappa B (NF-κB) mRNA and intercellular adhesion molecule-1 (ICAM-1) mRNA in hippocampus (by RT-PCR), and microscopic examination. Results Compared with group S, NDS at T_(1-3) was significantly increased, expression of NF-κB mRNA and ICAM-1 mRNA at T_(1-3) was up-regulated and serum concentrations of TNF-α at T_(1,2)and IL-1β at T_(1-3) were significantly increased in the other three groups (P < 0.05 or 0.01). Compared with group IR, NDS at T_(1-3) was significantly decreased, expression of NF-κB mRNA and ICAM-I mRNA at T_(1-3) was down-regulated and serum concentrations of TNF-α at T_(1,2)and IL-1βat T_(1-3) were significantly decreased in group F_(1,2) (P < 0.05 or 0.01). The expression of ICAM-1 mRNA at T_(2,3) was down-regulated and serum concentrations of IL-1β at T_2 significantly decreased in group F_2 compared with group F_1(P < 0.05 or 0.01). The histologic damage was significantly slighter in group F_(1,2) than in group IR and in group F_2 than in group F_1. Conclusion Pretreatment with flurbiprofen can attenuate global cerebral IR injury through inhibition of the inflammatory reaction in hippocampus in a dose-dependent manner in rats. Key words: Flurbiprofen;  Brain;  Reperfusion injury;  Hippocampus