COX-2抑制剂对大鼠局灶性脑缺血再灌注损伤的保护作用研究

目的观察选择性环氧合酶2(cyclooxygenase2,COX2)抑制剂尼美舒利(nimesulide)对大鼠局灶性脑缺血/再灌注损伤后神经功能缺陷、脑梗死体积及前列腺素E2(PGE2)含量的影响。方法用线栓法制作大鼠脑缺血/再灌注损伤模型,动物分别于缺血前30min、再灌注后6h、12h给予3个不同剂量尼美舒利(3、6和12mg/kg,ip)或等体积的溶媒。于再灌注后6、12、24h进行神经功能评分;采用TTC染色法测定脑梗死体积;应用ELISA法检测PGE2含量。结果尼美舒利呈剂量依赖性减少脑梗死体积并改善功能预后,与溶媒组比较有显著性差异;各尼美舒利治疗组脑梗死后PGE2含量和溶媒组相比显著降低。结论尼美舒利对缺血性脑损伤具有明显的保护作用,其保护作用可能与通过减少花生四烯酸环氧酶途径的代谢产物,从而抑制脑缺血后的炎症反应有关。

Protective effects of nimesulide on focal cerebral ischemia/reperfusion injury in rats

Objective To investigate the effects of nimesulide(selective cyclooxygenase-2 inhibitor)on the neurological deficits,infarct volumes and prostaglandin E_2(PGE_2)levels during focal cerebral ischemia/reperfusion injury in rats.Methods Animals were given three doses of nimesulide(3,6 and 12 mg/kg;ip.)or vehicle 30 min before experiment and 6 h,12 h after reperfusion.Rats subjected middle cerebral artery occlusion(MCAO)for 120 min using intraluminal filament model and neurological deficits examinations were performed at 6,12 and 24 h after reperfusion.After the last examination the animals were sacrificed,the infarct volumes were determined by TTC staining,and PGE_2 levels were also measured by means of ELISA.Results Nimesulide dose-dependently reduced infarct volume and improved functional recovery when compared to vehicle.Nimesulide significantly decreased the PGE2 accumulation after reperfusion.Conclusion Nimesulide has marked protective effects on ischemic brain damage in rats,and the inhibition of arachidonic acid metabolism and inflammatory response might be involved in the mechanism.