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目的:观察银杏叶提取物(EGb761)对血管性痴呆(VaD)大鼠空间学习记忆和海马N-甲基-D-天冬氨酸型离子型谷氨酸受体1型亚单位(NMDAR1)表达的影响。方法:采用四血管阻断法制备VaD大鼠模型,设立假手术组、模型组、尼莫地平组(10 mg/kg/d,灌胃30 d)和银杏叶提取物组(50 mg/kg/d,灌胃30 d)。利用Morris水迷宫检测大鼠空间学习记忆的改变,采用免疫组化和Western blot技术检测大鼠海马神经元NMDAR1蛋白水平的变化,实时荧光定量PCR技术检测大鼠海马NMDAR1的mRNA表达变化。结果:与假手术组相比,模型组大鼠水迷宫逃避潜伏期延长,撤后台靶象限平均探索次数减少(P<0.05),银杏叶提取物明显改善了VaD大鼠在Morris水迷宫中的学习记忆成绩(P<0.05);假手术组、尼莫地平组与银杏叶提取物组之间比较无统计学差异(P>0.05)。模型组大鼠的NMDAR1蛋白及其mRNA在海马CA1区的表达水平较假手术组明显降低(P<0.05);银杏叶提取物组大鼠海马的NMDAR1蛋白及mRNA表达水平较模型组明显升高(P<0.05)。结论:银杏叶提取物可以减轻脑缺血再灌注对海马CA1区神经元的损伤,这可能与上调海马组织内NMDAR1蛋白及mRNA的表达密切相关。
OBJECTIVE: To observe the effects of Ginkgo biloba extract (EGb761) on spatial learning and memory and the NMDA receptor subtype 1 (NMDAR1) The impact of expression. Methods: The VaD rat model was established by four-vessel occlusion method. The rats in model group, nimodipine group (10 mg / kg / d, gavage for 30 days) and ginkgo biloba extract group / d, gavage 30 d). Morris water maze was used to detect the changes of spatial learning and memory in rats. The changes of NMDAR1 protein in hippocampal neurons were detected by immunohistochemistry and Western blot. The mRNA expression of NMDAR1 was detected by real-time fluorescence quantitative PCR. Results: Compared with the sham operation group, the water maze of model rats prolonged the evasion latency and the number of exploration quadrats (P <0.05) decreased. The Ginkgo biloba extract significantly improved learning of VaD rats in Morris water maze (P <0.05). There was no significant difference between sham operation group, nimodipine group and Ginkgo biloba extract group (P> 0.05). NMDAR1 protein and mRNA expression in hippocampal CA1 region of model group were significantly lower than those of sham operation group (P <0.05); NMDAR1 protein and mRNA expression in hippocampus of Ginkgo biloba extract group was significantly higher than that of model group (P <0.05). CONCLUSION: Ginkgo biloba extract can relieve the neuronal damage of hippocampal CA1 area after cerebral ischemia-reperfusion, which may be closely related to the up-regulation of NMDAR1 protein and mRNA expression in hippocampus.