氟比洛芬酯预处理对大鼠全脑缺血/再灌注时脑组织TXA_2/PGI_2的影响

目的探讨氟比洛芬酯预处理对大鼠全脑缺血/再灌注损伤的影响。方法72只♂SD大鼠,体重250～350g,随机分为4组(n=18):假手术组(SH组)、模型组(Model组)、氟比洛芬酯5mg·kg-1组(F5组)和氟比洛芬酯10mg·kg-1组(F10组)。采用夹闭双侧颈总动脉20min合并低血压法建立全脑缺血/再灌注(I/R)模型。F5组和F10组分别于缺血前15min静注氟比洛芬酯5mg·kg-1+空白乳剂0.5ml.kg-1、氟比洛芬酯10mg·kg-1。于再灌注6、24、72h时行神经功能缺陷评分(NDS)、HE染色观察海马CA1区细胞损伤情况、放射免疫法测定额区皮质血栓素A2(TXA2)和前列环素(PGI2)含量。结果氟比洛芬酯5mg·kg-1组(F5组)或氟比洛芬酯10mg·kg-1组(F10组)预处理可明显减轻大鼠全脑缺血/再灌注后海马CA1区损伤,提高神经功能缺陷评分(NDS),降低脑组织中TXA2含量和TXA2/PGI2值,且F10组较F5组海马CA1区损伤更轻。结论氟比洛芬酯预处理可减轻全脑缺血/再灌注损伤,其机制可能与降低TXA2值和TXA2/PGI2值有关。

Effect of flurbiprofen axetil pretreatment on TXA2/PGI2 of brain tissue in rats subjected to global cerebral ischemia-reperfusion injury

Aim To investigate the effect of flurbiprofen axetil pretreatment on global cerebral ischemia-reperfusion injury in rats.Methods 72 Adult male Sprague-Dawley rats weighing 250~350 g were randomly divided into four groups:sham group(SH),global cerebral ischemia-reperfusion model group(Model),flurbiprofen axetil 5 mg·kg-1 group(F5)and flurbiprofen axetil 10 mg·kg-1 group(F10).Global cerebral ischemia was induced by 20 min occlusion of bilateral common carotid arteries combined with hypotension.In group F5 and F10 flurbiprofen axetil 5 mg·kg-1+blank emulsion 0.5 ml·kg-1 and 10 mg·kg-1 was injected iv at 15 min before ischemia respectively. The neurological deficit(NDS) was scored (0:normal,100:brain death) at 6,24 and 72 h of reperfusion by the same observer.Pathological changes in CA1 region of hippocampus were observed at 6,24 and 72 h of reperfusion through HE staining. Radioimmunoassay technique was used to determine TXA2 and PGI2 content of the brain tissue at 6,24 and 72 h of reperfusion.Results Pretreatment with flurbiprofen axetil 5 mg·kg-1 or flurbiprofen axetil 10 mg·kg-1 significantly reduced histopathological injury in CA1 region of hippocampus,improved neurological deficit score(NDS),reduced TXA2 content and TXA2/PGI2 of the brain tissue.Moreover,the effect of reducing histopathological injury in CA1 region of hippocampus in group F10 was better than that of group F5.Conclusion Pretreatment with flurbiprofen axetil can protect against global cerebral ischemia through inhibition of TXA2 content and TXA2/PGI2 of the brain tissue.