摘要目的 观察β-淀粉样蛋白(Aβ)和载脂蛋白E(apoE)4对大鼠海马胆碱乙酰转移酶(ChAT)的影响以及二者是否具有协同作用.方法 将雄性Wistar大鼠分为4组:对照组海马注射生理盐水,Aβ组注射Aβ1-40,apoE4组注射apoE4,Aβ+ apoE4组注射Aβ1-40+apoE4.水迷宫检测各组大鼠的学习记忆能力,原位杂交法检测海马CA1区ChAT的表达.结果 大鼠第5天的逃避潜伏期、跨台次数、ChAT mRNA PU值分别为:对照组(10.75 s±2.44 s,4.13 ±0.64,28.90±4.43)、apoE4组(23.88 s ±4.32 s,2.38 ±0.52,20.85±3.98)、Aβ组(43.50s±9.78 s,1.38±0.52,16.96 ±2.53)、A β+ apoE4组(70.63 s±10.04 s,0.75 ±0.71,13.01±2.21).apoE4组、Aβ组与对照组比较大鼠第5天的逃避潜伏期明显延长,跨台次数明显减少,差异有统计学意义(P＜0.01)；Aβ组与apoE4组比较,大鼠第5天的逃避潜伏期明显延长,跨台次数明显减少,差异有统计学意义(P＜0.01)；Aβ与apoE4之间存在交互作用(F=7.098,P＜0.01).apoE4组、Aβ组比对照组ChAT mRNA PU值下降明显(均P＜0.01)；Aβ组比apoE4组ChAT mRNA PU值下降明显(P ＜0.01)；Aβ+ apoF4组比对照组、apoE4组及Aβ组均下降明显(均P＜0.01)；Aβ与apoE4具有交互作用(P＜0.05).结论 (1)Aβ及apoE4均可损伤海马胆碱能系统,影响大鼠学习记忆能力；Aβ对海马胆碱能系统及学习记忆能力的损伤比apoE4严重.(2)Aβ与apoE4对海马胆碱能系统及学习记忆能力的损伤具有协同作用.

abstractsObjective To investigate the effects of beta-amyloid (Aβ) and apolipoprotein E4 (apoE4) on choline acetyl transferase (ChAT) in hippocampus and to explore possible the synergistic effect of both Aβ and apoE4.Methods Male Wistar rats were divided into four groups:control group,Aβ group,apoE4 group and Aβ + apoE4 group.Rats in different group received injection of normal saline,Aβ1-40,apoE4 and Aβ1-40 + apoE4,respectively,into bilateral hippocampus CA1 regions under the control of a brain stereotaxie apparatus.The learning-memory ability with the escape latency and the times of passing platform and the expression of ChAT in hippocampus CA1 regions were documented.Results The escape latency at fifth day and the times of passing platform and ChAT mRNA PU values were obtained for the control group (10.75 s±2.44 s,4.13 ±0.64,and 28.90 ±4.43),apoE4 group (23.88 s±4.32 s,2.38 ±0.52,and 20.85 ±3.98),Aβ group (43.50 s ±9.78 s,1.38 ±0.52,and 16.96 ±2.53),and Aβ+ apoE4 group (70.63 s± 10.04 s,0.75 ±0.71,and 13.01 ±2.21).Through 5 days of training all animals acquired learning-memory ability with the gradually shortened escape latency,although injection of Aβ1-40 and apoE4 all induced learning-memory damage,due to a significantly prolonged the escape latency at fifth day (P＜0.01) and markedly decreased the times of passing platform (P ＜ 0.01) in both Aβ and apoE4 group than in control group.An interaction between Aβ and apoE4 also was observed,with furtber prolonged escape latency(P ＜ 0.01).ChAT mRNA PU values were significantly lower in the Aβ group and apoE4 group than in the control group (P ＜ 0.01).Aβ and apoE4 demonstrated interaction in lowering ChAT mRNA level (P ＜ 0.05).Conclusions Both Aβ and apoE4 induce an injury to hippocampal cholinergic system and its learning-memory ability,in which Aβ and apoE4 have a synergistic effect in the initiation of such injury.