肌苷对脑缺血再灌注后COX-2表达的调节作用

目的 研究肌苷对大鼠脑缺血再灌注后COX-2mRNA及其蛋白表达影响，探讨其神经保护作用机制。方法 应用线栓法建立大鼠脑缺血再灌注动物模型，肌苷组缺血再灌注前腹腔注射肌苷（100mg/kg），假手术组和对照组同步注射相同剂量生理盐水。原位杂交法和免疫组织化学法检测大鼠脑缺血再灌注后COX-2 mRNA及蛋白的表达。结果 对照组皮质和纹状体区COX-2 mRNA表达于脑缺血再灌注6h开始增强，12h达高峰，持续1～3d，然后逐渐降低，至14d仍高于再灌注2h水平，同一时间点皮质区高于纹状体区。肌苷组COX-2 mRNA表达于脑缺血再灌注2h～14d较对照组显著减低（t=5．50～11．66，P〈0．01）。对照组皮质和纹状体区COX-2蛋白表达的变化趋势与COX-2 mRNA相似，但其高峰出现在24h，较COX-2 mRNA略延迟，且持续时间短，至7d已降至再灌注2h水平，同一时间点皮质区高于纹状体区。肌苷组COX-2表达于脑缺血再灌注2h～14d较对照组显著减低（t=3．27～18．14，P〈0．01）。结论 肌苷对脑缺血的保护作用可能是通过下调COX-2 mRNA及蛋白表达而实现的。

REGULATORY ROLE OF INOSINE ON EXPRESSION OF COX-2 FOLLOWING CEREBRAL ISCHEMIA REPERFUSION IN RATS

Objective To investigate the effects of Inosine on the cyclooxygenase-2 mRNA(COX-2(mRNA)) and protein expression in the brain of focal cerebral ischemia in rats. Methods The filament animal models of middle cerebral artery occlusion(MACO) and reperfusion were established with Sprague-Dawley rats,which were divided into the control group(saline solution was injected intraperitoneally) and the Inosine group(Inosine was injected intraperitoneally,100 mg/kg).Each group was subdivided into eight subgroups,with four rats in each.At 2 h,6 h,12 h,24 h,2 d,3 d,7 d,and 14 d after reperfusion of MACO,in situ hybridization and immunohistochemistery were used to detect the COX-2 mRNA and protein expression. Results The COX-2 mRNA positive cells occurred at 6 h,with the peak at 12 h,sustained 24 h-3 d after reperfusion,and gradually decreased to the level of reperfusion at 2 h on 14 d.There were more COX-2 mRNA positive cells in cerebral cortex than in striatum.Inosine significantly suppressed the COX-2 mRNA expression(t=5.50-11.66,P<0.01).The COX-2 protein expression pattern was similar to that of its mRNA,but the expression peak delayed at 24 h,lasted a short time,and then decreased to the level of reperfusion at 2 h on 7 d.There were more COX-2 positive cells in the cortex than in the striatum.Inosine significantly suppressed the COX-2 expression(t=3.27-18.14,P<0.01). Conclusion(Inosine may) down-regulate the level of COX-2 mRNA and its protein expression,and prevent brain tissue from hypoxic-ischemic damage after reperfusion of MACO.