【摘要】 目的:探讨艾地苯醌对血管性痴呆(VD)大鼠认知功能的作用,并初步探讨其机制。方法:SD大鼠60只随机均分为3组:假手术组、模型组和艾地苯醌组,各20只。采用改良双血管阻断(2-VO)法建立大鼠VD模型,艾地苯醌组大鼠腹腔注射艾地苯醌,10 mg/kg,1次/d,连续给药30 d;模型组及假手术组腹腔注射等量生理盐水。采用水迷宫评价各组大鼠学习、记忆能力;免疫组化测定海马生长相关蛋白-43(GAP-43)、突触素P38表达;透射电镜观察突触超微结构的改变。结果:模型组逃避潜伏期长于假手术组和艾地苯醌组(P<0.05),穿越原平台次数少于假手术组和艾地苯醌组(P<0.05);艾地苯醌组逃避潜伏期和穿越原平台次数与假手术组差异无统计学意义(P>0.05)。模型组GAP-43和触素P38蛋白的表达水平均低于其他2组(P<0.05);艾地苯醌组GAP-43和触素P38蛋白的表达水平均高于其他2组(P<0.05)。电镜下可见模型组大鼠海马区突触结构受损,艾地苯醌组大鼠海马组织区突触数量丰富,结构基本完整。结论:艾地苯醌可改善VD大鼠的学习和记忆功能,其机制可能与增强突触相关蛋白GAP-43和突触素P38的表达有关。更多还原

【Abstract】 Objective: To investigate the effects of idebenone on cognitive function and expression of growth associated protein-43(GAP-43) and synaptophysin P38 in the hippocampus of vascular dementia(VD) rats. Methods: Sixty SD rats were randomly divided into the sham operation group, model group, and idebenone group with 20 rats in each group. The VD rat model was established by modified 2-vessel occlusion(2-VO) method. Idebenone group rats were given intraperitoneal injections of idebenone at 10 mg/kg once per day for 30 consecutive days, and model group and sham operation group rats were given equivalent doses of normal saline. The differences in learning and memory capabilities were evaluated by water maze. The expression of GAP-43 and synaptophysin P38 in the hippocampus was measured by immunohistochemistry. The ultrastructure of synapses was observed by transmission electron microscopy.Results: The model group showed increased escape latency and decreased platform crossings in the water maze compared to those in the sham operation and idebenone groups(both P<0.05). The escape latency and platform crossings of the idebenone group and sham operation group showed no significant difference(P>0.05). Compared with that of sham operation group and idebenone group rats, the GAP-43 and synaptophysin P38 expression in the hippocampus of model group rats was decreased(P<0.05).Hippocampus expression of GAP-43 and synaptophysin P38 in idebenone group rats was increased compared to that of sham operation group and model group rats(P<0.05). Electron microscopy showed that in model group rats, synaptic structure in the hippocampus was damaged while in idebenone group rats,synapses in the hippocampus were abundant in quantity and complete in structure. Conclusion: Idebenone may improve learning and memory capabilities in VD rats via mechanisms that involve up-regulating GAP-43 and synaptophysin P38 expression.更多还原