CAJ | 학술논문

目的研究肌苷对大鼠脑缺血再灌注后COX-2 mRNA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6 h开始增强,12 h达高峰,持续1～3 d,然后逐渐降低,至14 d仍高于再灌注2 h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2 h～14 d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24 h,较COX-2 mRNA略延迟,且持续时间短,至7 d已降至再灌注2 h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2 h～14 d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.
목적연구기감대대서뇌결혈재관주후COX-2 mRNA급기단백표체영향,탐토기신경보호작용궤제.방법응용선전법건립대서뇌결혈재관주동물모형,기감조결혈재관주전복강주사기감(100mg/kg),가수술조화대조조동보주사상동제량생리염수.원위잡교법화면역조직화학법검측대서뇌결혈재관주후COX-2 mRNA급단백적표체.결과대조조피질화문상체구COX-2 mRNA표체우뇌결혈재관주6 h개시증강,12 h체고봉,지속1～3 d,연후축점강저,지14 d잉고우재관주2 h수평,동일시간점피질구고우문상체구.기감조COX-2 mRNA표체우뇌결혈재관주2 h～14 d교대조조현저감저(t=5.50～11.66,P<0.01).대조조피질화문상체구COX-2단백표체적변화추세여COX-2 mRNA상사,단기고봉출현재24 h,교COX-2 mRNA략연지,차지속시간단,지7 d이강지재관주2 h수평,동일시간점피질구고우문상체구.기감조COX-2표체우뇌결혈재관주2 h～14 d교대조조현저감저(t=3.27～18.14,P<0.01).결론기감대뇌결혈적보호작용가능시통과하조COX-2 mRNA급단백표체이실현적.
Objective To investigate the effects of Inosine on the cyclooxygenase-2 mRNA (COX-2mRNA) 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.