白藜芦醇对APP/PS1双转基因小鼠学习记忆能力的改善作用
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摘要
目的探讨白藜芦醇对APP/PS1双转基因小鼠学习记忆能力的改善作用。方法 50只小鼠随机分为模型组、多奈哌齐组(10 mg/kg)及白藜芦醇低、中、高剂量组(25、50、100 mg/kg),每组10只,10只C57BL/6小鼠作为对照组,各组灌胃给药40 d。Morris水迷宫定位航行实验和空间探索实验分别检测小鼠学习记忆能力,免疫荧光法检测小鼠海马区星形胶质细胞表达,RT-PCR法和ELISA法分别检测小鼠海马区IL-1β、IL-6、TNF-αmRNA表达和水平。结果与模型组比较,白藜芦醇组缩短逃避潜伏期,增加穿越平台次数和目标象限停留时间,降低星形胶质细胞表达及IL-1β、IL-6、TNF-αmRNA表达和水平,以中、高剂量组更显著(P<0. 05,P<0. 01)。结论白藜芦醇可改善APP/PS1双转基因小鼠学习记忆能力,其机制可能与抑制星形胶质细胞增生和炎性因子释放、减轻炎症反应有关。
AIM To explore the improvement effects of resveratrol on learning and memory abilities of double transgenic APP/PS1 mice. METHODS Fifty mice randomly assigned into model group, donepezil group( 10 mg/kg) and resveratrol low-dose,medium-dose,high-dose groups( 25,50,100 mg/kg),ten mice in each group,were intragastrically administered with the corresponding agents for 40 d,and ten C57BL/6 mice were recruited into control group. Mouse learning and memory activities were detected by Morris water maze place navigation test and spatial probe test,respectively. Astrocyte expression in mouse hippocampal area was detected by immunofluorescence. IL-1β,IL-6,TNF-α mRNA expressions and levels in mouse hippocampal area were determined by RT-PCR and ELISA,respectively. RESULTS Compared with the model group,the resveratrol groups demonstrated shortened escape latent period,increased platform-crossing frequency and target quadrant residence time,decreased astrocyte expression and IL-1β,IL-6,TNF-α mRNA expressions and levels,especially for the mediumdose,high-dose groups( P<0. 05,P<0. 01). CONCLUSION Resveratrol can improve the learning and memory abilities of double transgenic APP/PS1 mice,whose mechanisms may contribute to inhibiting astrocyte hyperplasia and inflammatory factor release,and alleviating inflammatory reactions.
AIM To explore the improvement effects of resveratrol on learning and memory abilities of double transgenic APP/PS1 mice. METHODS Fifty mice randomly assigned into model group, donepezil group( 10 mg/kg) and resveratrol low-dose,medium-dose,high-dose groups( 25,50,100 mg/kg),ten mice in each group,were intragastrically administered with the corresponding agents for 40 d,and ten C57BL/6 mice were recruited into control group. Mouse learning and memory activities were detected by Morris water maze place navigation test and spatial probe test,respectively. Astrocyte expression in mouse hippocampal area was detected by immunofluorescence. IL-1β,IL-6,TNF-α mRNA expressions and levels in mouse hippocampal area were determined by RT-PCR and ELISA,respectively. RESULTS Compared with the model group,the resveratrol groups demonstrated shortened escape latent period,increased platform-crossing frequency and target quadrant residence time,decreased astrocyte expression and IL-1β,IL-6,TNF-α mRNA expressions and levels,especially for the mediumdose,high-dose groups( P<0. 05,P<0. 01). CONCLUSION Resveratrol can improve the learning and memory abilities of double transgenic APP/PS1 mice,whose mechanisms may contribute to inhibiting astrocyte hyperplasia and inflammatory factor release,and alleviating inflammatory reactions.
引文
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[13]李少恒,教亚男,姚璎珈,等.蛇床子素对感染APP基因的神经元突触的保护作用[J].中国药理学通报,2015,31(10):1383-1388.
[14]汤双红,肖佳欢,王芸,等.“益肾调督”电针法对Aβ1-42诱导的痴呆模型大鼠海马中Aβ相关清除酶的影响[C]//第十九届中国科协年会——分11针灸脑科学研究高层论坛论文集.长春:中国科学技术协会,吉林省人民政府,2017.
[15]金美玉,吴建龙,金清华,等.急性应激大鼠的海马DG区兴奋性氨基酸在空间学习记忆中的变化[J].中国实验诊断学,2017,21(5):893-896.
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[17]杨同章,沈伟.阿尔茨海默病与炎症[J].中国中医药现代远程教育,2012,10(19):109-111.
[18]蔡志友,吴芳,晏勇.星形胶质细胞与阿尔茨海默病[J].重庆医学,2009,38(6):733-735.
[2] Wilcock D M,Gharkholonarehe N,Van Nostrand W E,et al.Amyloid reduction by amyloid-beta vaccination also reduces mouse tau pathology and protects from neuron loss in two mouse models of Alzheimer’s disease[J]. J Neurosci,2009,29(25):7957-7965.
[3] Malthankar-Phatak G H,Lin Y G,Giovannone N,et al. Amyloid deposition and advanced age fails to induce Alzheimer’s type progression in a double knock-in mouse model[J]. Aging Dis,2012,3(2):141-155.
[4]王华丽,于欣.中国阿尔茨海默病的流行病学现状[J].中华全科医师杂志,2006,5(6):358-360.
[5]解恒革.阿尔茨海默病的药物治疗[J].世界临床药物,2017,38(2):83-87.
[6]王睿,王琪,金明顺,等.白藜芦醇对围绝经期抑郁症模型小鼠行为学影响及机制分析[J].中国实验方剂学杂志,2017,23(4):132-139.
[7]张艳茹,贺永贵,伊红丽,等.白藜芦醇神经系统保护作用的研究进展[J].河北联合大学学报(医学版),2014,16(2):162-164.
[8]刘贵珊,杨博,张泽生,等.白藜芦醇对D-半乳糖致衰老小鼠学习记忆能力和脑组织抗氧化能力的影响[J].食品科学,2014,35(5):204-207.
[9]王宇,黄清,董明睿,等.白藜芦醇对β-淀粉样蛋白致小鼠学习记忆障碍改善作用的机制研究[J].中风与神经疾病杂志,2015,32(6):518-521.
[10]郜娜,杨庆宇.白藜芦醇对高血脂模型小鼠的预防作用和对模型金黄地鼠的改善作用研究[J].中国药房,2017,28(31):4393-4397.
[11]靳艳君.五味子水提取液对APP/PS1小鼠大脑皮层神经细胞保护作用研究[J].辽宁中医药大学学报,2017,19(4):30-33.
[12]孔亮,姚璎珈,教亚男,等.蛇床子素对机械性脑损伤小鼠的抗炎抗凋亡作用研究[J].中国药理学通报,2015,31(7):999-1004.
[13]李少恒,教亚男,姚璎珈,等.蛇床子素对感染APP基因的神经元突触的保护作用[J].中国药理学通报,2015,31(10):1383-1388.
[14]汤双红,肖佳欢,王芸,等.“益肾调督”电针法对Aβ1-42诱导的痴呆模型大鼠海马中Aβ相关清除酶的影响[C]//第十九届中国科协年会——分11针灸脑科学研究高层论坛论文集.长春:中国科学技术协会,吉林省人民政府,2017.
[15]金美玉,吴建龙,金清华,等.急性应激大鼠的海马DG区兴奋性氨基酸在空间学习记忆中的变化[J].中国实验诊断学,2017,21(5):893-896.
[16] Coomaraswamy J,Kilger E,W9lfing H,et al. Modeling familial Danish dementia in mice supports the concept of the amyloid hypothesis of Alzheimer’s disease[J]. Proc Natl Acad Sci USA,2010,107(17):7969-7974.
[17]杨同章,沈伟.阿尔茨海默病与炎症[J].中国中医药现代远程教育,2012,10(19):109-111.
[18]蔡志友,吴芳,晏勇.星形胶质细胞与阿尔茨海默病[J].重庆医学,2009,38(6):733-735.