【摘要】 目的观察新型PPARα激动剂油酰乙醇胺(oleoyleth-anolamide,OEA)对小鼠局灶性脑缺血损伤的保护作用及特点。方法线栓法制备小鼠大脑中动脉栓塞模型诱导脑缺血。OEA(10、20、40mg·kg-1)在术前3d开始每天灌胃给药1次;或在缺血前0.5h、1h、再灌注同时、再灌后1h,各单次灌胃给予OEA40mg·kg-1。脑缺血1.5h,再灌注24h后,测定小鼠神经功能缺失评分、脑梗死体积、脑水肿等评定脑缺血损伤的指标。结果OEA(20、40mg·kg-1)术前多次给药及OEA(40mg·kg-1)缺血前0.5h或再灌注同时单次给药可明显改善小鼠神经功能损伤,减小脑梗死体积和减轻脑水肿程度,且以再灌注同时单次给药效果最为明显。结论OEA剂量及时间依赖性的保护小鼠局灶性脑缺血急性损伤,有效剂量为20mg·kg-1和40mg·kg-1,最佳治疗时间点为再灌注同时。更多还原

【Abstract】 Aim To investigate the effect of oleoylethanolamide (OEA),a new PPARα agonist,on focal cerebral ischemia in mice.Methods Transient focal cerebral ischemia in mice was induced by middle cerebral artery occlusion for 1.5 h. OEA was orally administered either with multiple doses (10,20,40 mg·kg-1) once a day for 3 days before ischemia or single dose (40 mg·kg-1) at 0.5 h before or 1 h before ischemic,the same time of reperfusion or 1 h after reperfusion respectively.Neurological deficit score,infarct volume and brain edema were determined.Results Pretreatment with multiple doses (20,40 mg·kg-1) of OEA before ischemia or single dose (40 mg·kg-1) of OEA at 0.5 h before ischemia or at the same time of reperfusion significantly attenuated neurological deficit score,decreased infarct volume and alleviated brain edema,and the treatment at the time of reperfusion had the most marked effect.Conclusion Oleoylethano-lamide has a dose-and time-dependent neuroprotective effect on the injury in the acute phase of transient focal cerebral ischemia in mice,with effective doses of 20 mg·kg-1 and 40 mg·kg-1 and the optimal therapeutic time point of the same time of reperfusion.更多还原