摘要
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(100 mg/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。
Objective To investigate the effects of Inosine on the cyelooxygenase-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, S d, 7 d, and 14 d after reperfusion of MACO, in situ hybridization and immunohistoehemistery 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. Inoslne 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.
出处
《青岛大学医学院学报》
CAS
2006年第1期13-17,共5页
Acta Academiae Medicinae Qingdao Universitatis
基金
SupportedbyNaturalScienceFundofShan-dongProvince(Y2001C04)
