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作 者:闫恩志[1] 范莹[1] 刘卓[1] 刘婉珠[2] 金英[1]
机构地区:[1]辽宁医学院药理学教研室,锦州121001 [2]辽宁医学院机能实验中心,锦州121001
出 处:《中药药理与临床》2013年第1期41-44,共4页Pharmacology and Clinics of Chinese Materia Medica
基 金:辽宁省教育厅科学研究项目(L2012310);辽宁省教育厅创新团队项目(LT 2010064)
摘 要:目的:研究阿魏酸钠(sodium ferulate,SF)对脂多糖(lipopolysaccharide,LPS)所致的大鼠学习记忆障碍的改善作用及机制。方法:大鼠每天ig给予SF(50,100 mg/kg),对照组和LPS模型组分别ig给予生理盐水,3w后,侧脑室注射5μl LPS(1.0mmol/L),对照组注射等量生理盐水。脑室注射后第2 d进行Morris水迷宫实验,第7 d,快速取海马CA1区,Western蛋白印迹方法观察磷酸化PDK1、Akt、GSK-3β蛋白表达。结果:脑室内注射LPS大鼠出现明显的空间学习记忆障碍,表现为逃避潜伏期和游泳路程较生理盐水对照组明显延长,在原平台象限游泳时间占总时间的百分比明显降低,同时伴有海马磷酸化PDK1、Akt和GSK-3β蛋白表达降低,SF(50,100 mg/kg)能对抗大鼠的这一行为学及蛋白表达改变。结论:SF通过上调磷酸化GSK-3β表达改善LPS所致大鼠学习记忆障碍。Objective:To observe the improving effects and mechanismof sodium ferulate(SF) on learning and memory ability after intracerebroventricular injection of lipopolysaccharide.Methods:Fourty Sprague-Dawley rats were randomly divided into four groups:control;LPS;LPS+SF 50 mg/kg;LPS+ SF100 mg/kg.Rats were given SF(50,100 mg/kg)with ig method for 3 weeks,then,rats were iniected intracerebroventricularly with LPS 5 μl(1.0 mmol/L),the control group were injected with saline of the same volume.Two days later,Morris water maze was used to measure the spatial learning and memory ability of rats,seven days after injection,Western blotting was used to determine the expression of phospho-PDK1,phospho-Akt and phospho-GSK-3β protein.Results:Intracerebroventricular injection of LPS in rats resulted in learning and memory impairments shown by longer escape latence and distance,also shown by decreased percentage of time spent in the target quadrant.These behavioral dysfunctions were accompanied by the decreased levels of phospho-PDK1,phospho-Akt and phospho-GSK-3β protein,all of these changes can be reversed by SF(50,100 mg/kg).Conclusion:Oral administration of SF(50,100 mg/kg) markedly improved LPS-induced the learning and memory dysfunction by increasing phospho-GSK-3β protein expression.
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