清开灵对快速老化痴呆小鼠学习记忆能力的影响及作用机制研究

作者	单位
邱蕾	北京师范大学认知神经科学与学习国家重点实验室
郑璐	北京师范大学认知神经科学与学习国家重点实验室
张瑶	北京师范大学认知神经科学与学习国家重点实验室
冯天骄	北京师范大学认知神经科学与学习国家重点实验室
于建春	天津中医药大学第一附属医院
张占军	北京师范大学认知神经科学与学习国家重点实验室
王永炎	中国中医科学院临床基础医学研究所

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中文摘要:

目的探讨清开灵对快速老化痴呆小鼠(senescence accelerated mouse-prone/8,SAMP8)学习记忆能力、全脑神经递质及磷脂酰肌醇3激酶激活的丝氨酸/苏氨酸蛋白激酶B磷酸化(phosphatidylinositol 3-kinase/protein kinase B,PI3K/AKT)信号通路的影响。方法将SAMP8老化鼠随机分为模型组、清开灵组[1.3mL/(kg·d)]及安理申组[0.58 mg/(kg·d)],治疗90天;抗快速老化亚系小鼠(senescence acceleratedmouse-resistance/1,SAMR1)作为对照组。采用水迷宫方法检测小鼠学习记忆能力,以高效液相电化学法检测小鼠全脑乙酰胆碱(ACh)及单胺类神经递质含量,蛋白质印迹法(Western-blot)测定脑Gab1(Grb2-associatedbinder-1)、AKT、473位点丝氨酸磷酸化蛋白激酶B(phospho-serine/threonine protein kinase B,pAKT473)的蛋白表达。结果与对照组SAMR1鼠比较,模型组SAMP8小鼠在隐平台试验和反向试验第3天潜伏期显著升高(P<0.05,P<0.01),ACh、5-羟色胺(5-HT)水平显著降低(P<0.01,P<0.05),Gab1蛋白表达水平显著降低(P<0.01)。给药后,清开灵组小鼠在第2～5天隐平台试验和反向试验中潜伏期较模型组显著降低(P<0.05),ACh、5-HT含量明显升高(P<0.05),Gab1蛋白表达水平显著增加(P<0.01),AKT蛋白磷酸化水平显著增加(P<0.05)。结论清开灵能改善AD模型小鼠的学习记忆能力,这一作用可能与其提高脑内ACh、5-HT的水平,激活PI3K/AKT通路有关。

英文摘要:

Objective To investigate the influence of Qingkailing(QKL)on learning and memory abilities, global neurotransmitter and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway of senescence accelerated mouse-prone/8(SAMP8)mice with Alzheimer’s dementia(AD).Methods SAMP mice were modeled and divided into the model group,the QKL group and the doneppezil hydrochloride group,all treated for 90 days.And a control group was set up with senescence accelerated mouse-resistance/1(SAMR1) mice.Morris water maze was used to test the learning and memory abilities of mice;contents of acetylcholine (Ach)and monoamine neurotransmitters in brain were measured by HPLC;levels of Grb2-associated binder-1 (Gab1),AKT and phospho-serine/threonine protein kinase B(PAKT473)were evaluated by Western-blot.Results Compared with the control group,in the model group,the average escape latency detected by hidden platform trial and reverse frial on the 3rd day was higher(P<0.01);levels of Ach,5-hydroxytryptamine(5-HT)and Gab1 were lower(P<0.01,P<0.05 and P<0.01),respectively.As compared with the model group,the escape latency(within the 2nd to 5th day)decreased(P<0.01),levels of Ach and 5-HT increased(P<0.05), and Gab1 protein expression increased(P<0.01)in the QKL treated group after treatment,in addition,the level of phosphorylated AKT protein significantly increased(P<0.05).Conclusion QKL could improve the learning and memory ability of AD model mice,which is probably related to its function in increasing cerebral Ach,5-HT and activating PI3K/AKT pathway.

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