NR_1反义抑制剂对局灶性脑缺血作用的初步研究

Effects of antisense oligodeoxynucleotides to NMDA-R_1 receptor on cerebral infarction in rats

目的 探讨NR1反义寡核苷酸对局灶性脑缺血的治疗作用。方法 于大鼠大脑中动脉闭塞后2小时、2 4小时分别经侧脑室注射磷酸缓冲液 (PBS)、错义寡核苷酸 (MSODN)及反义寡核苷酸 (ASODN) ,然后在不同时间点进行神经功能缺损评分 ,术后第 5天进行Nissl染色、TTC染色及梗死体积比测定。结果 各组局灶性脑缺血的神经功能缺损评分无显著性差异 ;反义寡核苷酸治疗组的梗死体积比显著低于单纯缺血组 ;反义寡核苷酸治疗组海马各区神经元损伤轻 ,神经元丢失相对较少。结论 局灶性脑缺血后侧脑室注入NR1反义寡核苷酸 ,可以减轻缺血脑组织病理学损害 ,具有脑保护作用。

Objeictive To evaluate the treatment effects of antisense oligodeoxynucleotides (ASODN) to NMDA-R 1 rceptor on brain injury in experimental reversible middle cerebral artery occlusion(MCAO).Methods The different drugs such as PBS,MSODN and ASODN were injected intracerebroventricularly at the 2nd hour and 24th hour after MCAO.Neurological scores were assessed at the 2nd hour,24th hour,and on the 2nd day,3rd day,4th day,5th day after MCAO.The rats were sacrificed on the 5th day after MCAO.Then TTC staining and Nissl staining were performed.The numerial density(ND) of Nissl staining neurons in hippocampals and the percent of infarct volume in hemisphere volume were measured by CIMAS image analysis system.Results The neurological score for the daily examinations was not significantly different among these groups,the percent of infarct volume in hemisphere volume was markedly reduced in ASODN group (32.82±6.89)versus MCAO group(41.22±4.38),and the ND of Nissl staining neurons were markedly decreased after MCAO,but in ASODN group degeneration or necrosis of neurons greatly alleviated.Conclusion NR 1 ASODN could attenuate the neuron degeneration,reduce the focal infarct volume produced by MCAO and play a brain protective role against ischemic injury.