塞来昔布对大鼠局灶性脑缺血再灌注的保护作用及机制研究

The study on the action mechemism of Celecoxib on focal cerebral ischemic reperfusion in rats

目的探讨塞来昔布对大鼠局灶性脑缺血再灌注损伤的保护作用及可能机制。方法采用线栓法制作Wistar大鼠大脑中动脉闭塞(MCAO)90min再灌注模型,分为假手术组、等渗盐水组塞来昔布12.5mg/kg治疗组及塞来昔布25mg/kg治疗组。缺血后30min灌胃给予等渗盐水或两种剂量(12.5mg/kg或25mg/kg)的塞来昔布,检测各分组大鼠缺血侧额顶部皮质在再灌注不同时点前列腺素代谢物、丙二醛(malondialdehyde,MDA)含量、超氧化物歧化酶(superoxide dismutase,SOD)活性的动态变化。结果(1)塞来昔布12.5mg/kg治疗及塞来昔布25mg/kg治疗均可明显缩小脑I/R时脑损伤范围,减轻脑水肿程度;(2)塞来昔布12.5mg/kg治疗和塞来昔布25mg/kg治疗均能不同程度的降低前列腺素E2(Prostaglandin E2,PGE2)、血栓素B2(Thromboxane B2,TXB2)、6-酮-前列腺素F1α(6-ketto-prostaglandin F1α,6-K-PGF1α)在缺血侧额顶部皮质中聚集,同时使TXB2/6-K-PGF1α比值下降。也能不同程度的降低MDA含量,提高SOD活性。结论COX-2抑制剂可能通过减少PGE2的集聚,改善TXB2/6-K-PGF1α比值,减少氧自由基的产生,提高SOD活性而发挥脑保护作用。

Objective To explore the protective mechamism of Celecoxib in rats subjected to focal ischmia/ reperfusion. Methods MCAO for 1.5h reperfusion Wistar rats models were performed with the photothrombotic occlusion method which were randomly divided into sham-operation group,Vehicle group,Celecoxib 12. 5mg/kg group and Celecoxib 25mg/kg group. Saline or different doses of Celecoxib were administrated to rats respectively after 30rain ischemia. Observed the effect of Celecoxib by detecting the dynamic changes of metabolitic production of prostaglandin, MDA and SOD in frontal and parietal cortexs in rats among different timepoint and different groups. Results （1）The cerebral pathologic injury and cerebral edema were distinctly alleviated after rats were treated with Celecoxib. （2）Both 12.5mg/kg and 25mg/kg Celecoxib could reduce the accumulation of PGE2,TXB2 and 6-K-PGF1α in frontal and parietal cortexs to some extent,but at the same time the ratio of TXB2and 6-K-PGF1α dropped. The content of MDA was decreased but that of SOD increased. Conclusions Celecoxib provided protection against CIRI possibly by reducing the accumulation of PGE2,the production of oxygen radicals ,altering the ration between TXB2 and 6-K-PGF1α, and increasing the activity of SOD.