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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 mechanism of N-methyl-D-aspartate receptor 1 (NMDAR1) antisense inhibitor (ASODN) in the treatment of acute cerebral infarction. Methods Koizumi’s suture method was used to make re-flow MCAO rat model. Forty male Wistar rats aged 8-12 months were randomly divided into 4 groups: (1) MCAO group; (2) MCAO + PBS group; (3) MCAO + MSODN group; (4) MCAO + ASODN group. The experimental groups were given intracerebroventricular injection 2h and 24h after MCAO, respectively. Animals were sacrificed on day 5 after MCAO, and brain tissues were harvested for detection of NMDAR1 immunohistochemistry and NMDAR1 mRNA in situ hybridization. The test results were quantitatively analyzed by CMIAS image analysis system. Results (1) The number density and optical density of NMDAR1 positive cells in CA1, CA3 and DG of ASODN group were significantly lower than that of MCAO group. (2) The number density of NMDAR1 mRNA positive cells in hippocampus and cerebral cortex There was no significant difference between optical density and MCAO group. Conclusion NMDAR1 antisense inhibitor may play a major role in the protein translation process of NMDAR1 gene (cytoplasm mechanism), inhibit the production of NMDAR1 in NMDAR1 neurons, decrease the number and function of NMDAR1, and reduce the delayed neuronal necrosis after ischemia. Achieve brain protection.