肌苷对大鼠脑缺血再灌注后生长相关蛋白基因表达和神经功能恢复的影响

Effect of Inosine on Expression of GAP-43 mRNA and Recovery of Neurological Function After Cerebral Ischemia Reperfusion in Rats

目的:探讨肌苷对脑缺血再灌注后中枢神经再生的作用。方法:应用线栓法建立大脑中动脉闭塞(MCAO)缺血再灌注模型,腹腔注射肌苷治疗,采用Bederson等神经功能评分法评定神经功能的恢复,原位杂交技术检测脑缺血再灌注后2h、12h、1d、2d、3d、7d、14d脑组织GAP-43 mRNA的表达。结果:对照组缺血侧GAP-43 mRNA表达皮质区除1 d和14 d外、纹状体区除2 h和14 d外各时间点均明显高于假手术组(P<0.05)。肌苷治疗组较对照组GAP-43 mRNA表达在皮质区于再灌注2 h-过性下降,12 h升高;在纹状体区12 h升高,7 d再次升高;神经功能恢复于再灌注7-14 d有显著改善(P<0.05)。结论:肌苷可促进大鼠脑缺血再灌注后神经功能恢复,其作用机制可能是通过调节与神经轴突再生有关的GAP-43 mRNA表达而实现的。

Objective: To explore the effect of inosine on the regeneration of central nervous system after cerebral ischemia reperfusion in rats. Methods: Cerebral ischemia reperfusion models of middle cerebral artery occlusion( MCAO) were established in rats by intraluminal occlusion, and then they were treated with intraperitoneal injection of inosine. The recovery of neurological function was evaluated according to the scores of neurological function by Bederson and his colleagues, and the expressions of GAP-43 mRNA at 2 h, 12 h, on day 1, 2, 3, 7, 14 after ischemia reperfusion in rats were detected by in situ hybridization technique. Results: GAP-43 mRNA expression on the ischemic sides in the control group was significantly higher than that in the sham-operated group (P <0. 005), except for the cortical areas on day 1, 14 and the striatum areas at 2 h and on day 14. In comparison with the inosine group, GAP-43 mRNA expression in the control group decreased transiently at 2 h and increased at 12 h, but increased again at 12 h and on day 7 in striatum areas, and the neurological function improved significantly form day 7 to 14 (P < 0.05). Conclusion: Inosine can improve the neurological function after ischemia reperfusion in rats and its acting mechanism might be due to the upregulation of GAP-43 mRNA which is correlated with the axonal regeneration.