N-甲基-D-天冬氨酸受体_1反义抑制剂治疗局灶性脑缺血作用机制的实验研究  

Effects of antisense oligodeoxynucleotides on NMDAR_1 in cerebral infarction in rats

作　　者：王云甫[1] 余绍祖[2] 范华燕[1] 

机构地区：[1]湖北省郧阳医学院附属太和医院神经科 [2]武汉大学人民医院神经科

出　　处：《卒中与神经疾病》2003年第1期16-19,共4页Stroke and Nervous Diseases

摘　　要：目的　探讨N 甲基 D 天冬氨酸受体1(NMDAR1)反义抑制剂 (ASODN)治疗急性脑梗死的作用机制。方法　采用Koizumi’s线栓法制作可复流MCAO大鼠模型。4 0只 8～ 12月龄健康、雄性Wistar大鼠随机分为 4组 :(1)MCAO组 ;(2 )MCAO +PBS组 ;(3)MCAO +MSODN组 ;(4)MCAO +ASODN组。实验各组分别于MCAO后 2h、2 4h经侧脑室注射给药。MCAO后第 5天处死动物 ,取脑组织进行NMDAR1免疫组织化学及NMDAR1mRNA原位杂交检测。检测结果经CMIAS图像分析系统进行定量分析。结果　(1)ASODN治疗组NMDAR1阳性细胞在海马CA1区、CA3 区及DG区的数密度、光密度显著低于MCAO组 ;(2 )ASODN治疗组NMDAR1mRNA阳性细胞在海马各区及大脑皮层的数密度、光密度与MCAO组无显著差异。结论　NMDAR1反义抑制剂可能主要作用于NMDAR1基因的蛋白翻译过程 (胞浆机制 ) ,抑制缺血后神经元NMDAR1的产生 ,下调NMDAR1的数量及功能 ,减轻缺血后迟发性神经元坏死 ,达到脑保护作用。Objective To investigate the effects of antisense oligodeoxynucleotides (ASODN) on NMDRR 1 in cerebral infarction in rats.Methods Reversible middle cerebral artery occlusion (MCAO) rats were induced with the intraluminal suture occlusion method created by Koizumi. 40 male Wistar rats, 280 to 380 g, were divided randomly into 4 groups:(1) MCAO group; (2) MCAO plus phosphate buffered saline (PBS) group; (3) MCAO plus missense oligodeoxynucleotide (MSODN) group; (4) MCAO plus ASODN group. The different drugs were injected intraventricularly at 2nd hour and 24th hour after MCAO in group B, C and D. The rats were sacrificed on 5th day after MCAO. Then NMDAR 1 immunchistochemistry and NMDAR 1 mRNA in situ hybridization were preformed. The numeral density (ND) and optical density (OD) of all positive neurons in hippocampus and cerebral cortex were measured by CMIAS image analysis system. The data were analyzed by SPSS 8.0 statistical software.Results (1) The ND and the OD of NMDAR 1 positive neurons in hippocampal CA 1, CA 3 or cortex in group D were greatly lower than that in group A, B or C; (2) The ND and the OD of NMDAR 1 mRNA positive neurons in hippocampus and cerebral cortex had no significant difference between group D and A. Conclusion The study suggested NMDAR 1 ASODN selectively inhibited the translation of NMDAR 1 and down regulated the expression of NMDA receptors, which could attenuate the neuron degeneration and play a brain protective role against ischemic injury.

关 键 词：实验研究 N-甲基-D-天冬氨酸受体1反义抑制剂 治疗 局灶性脑缺血 

分 类 号：R743.31[医药卫生—神经病学与精神病学]