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

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(P0.05,P0.01),ACh、5-羟色胺(5-HT)水平显著降低(P0.01,P0.05),Gab1蛋白表达水平显著降低(P0.01)。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(P0.05),ACh、5-HT含量明显升高(P0.05),Gab1蛋白表达水平显著增加(P0.01),AKT蛋白磷酸化水平显著增加(P0.05)。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。

Effect and Mechanism of Action of Qingkailing on Learning and Memory Capacity of SAMP8 Mouse

Objective To investigate the influence of Qingkailing （QKL） on leaming 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-HTand activating PI3K/AKT pathway.