非甾体类抗炎药对局灶性脑缺血再灌注后炎症反应及黏附分子表达的影响

目的 探讨消炎痛和美洛昔康对再灌注后脑损伤的影响及作用机制.方法 线栓法制作大鼠大脑中动脉缺血模型（MCAO）.用免疫组化方法观察脑组织ICAM-1、E-选择素的表达.白细胞髓过氧化物酶（MPO）检测试剂盒检测MPO活性.用放射免疫方法检测PGE2的浓度.TTC染色观察梗死范围.结果 消炎痛和美洛昔康早期给药,都能减小皮层梗死体积.再灌注后4h给药,对梗死体积都无明显影响.再灌注后缺血侧皮层和纹体PGE2浓度明显升高,MPO活性增高,消炎痛和美洛昔康均能降低皮层和纹体区PGE2的水平,明显减少ICAM-1和E-选择素阳性血管数,降低皮层MPO活性.结论 消炎痛和美洛昔康早期给药能减小皮层的梗死体积,这种脑保护作用与抑制内皮黏附分子的表达,减轻再灌注后炎症反应.随着再灌注时间的延长,这种保护作用减弱.

The influence of NSAIDs on the inflammatory injury and the expression of adhesion molecules after focal ischemia and reperfusion

Objective To study the effect of indomethacin and meloxicam on inflammatory injury after cerebral ischemia and reperfusion.Methods The focal cerebral ischemia and reperfusion model was made by suture occlusion of right middle cerebral artery.The rats were randomly assigned to six groups:sham operated group,reperfusion group,indomethacin treatment groups(X0h and X4h) and Meloxicam treatement groups(M0h and M4h).The expression of ICAM-1,E-selectin were detected by immunohistochemical method.MPO kit was applied to detect MPO activity.PGE2 was detected by3H- PGE2 RIA Kit.The area of infarct was detected by TTC staining.Results Treatment with indomethacin and meloxicam right after reperfusion,decreased the infarct size in the cortex,whereas treatment 4 hours after reperfusion did not.Twenty-two hours after reperfusion,the concentration of PGE2 increased significantly.Both indomethacin and meloxicam attenuated the increase of PGE2 in the ipsilateral cortex and striatum,decreased the activity of MPO and the number of ICAM-1 and E-selectin positive vessels.Conclusion Both indomethacin and meloxicam treatment right after reperfusion have neuroprotective effect,at least partly by inhibiting endothelial adhesion molecules expression,thus relieving inflammatory reaction.