己酮可可碱和咯利普兰对淀粉样β蛋白诱导脑损伤后学习记忆功能的影响

Effects of pentoxifylline and rolipram on learning and memory abilities after brain impairment induced by amyloid β-protein

目的探讨磷酸二酯酶抑制剂对淀粉样β蛋白(Aβ)诱导的脑损伤大鼠学习记忆功能的改善作用及可能机制。方法SD大鼠分为假手术对照组、模型组、己酮可可碱(PTX)16.5mg.kg-1组和咯利普兰1mg.kg-1组。模型组及给药组大鼠两侧海马内分别注射Aβ25-355μL,术后24h给药组ip给药,每日1次,连续14d。给药7d后进行避暗实验,14d后进行Morris水迷宫实验观察行为学变化。之后处死大鼠,用放射免疫法测定海马组织cAMP含量。结果与模型组比较,PTX组和咯利普兰组大鼠在避暗实验中潜伏期明显延长,在水迷宫实验中寻台时间明显缩短,海马组织cAMP水平显著升高。结论升高脑内cAMP水平可能是磷酸二酯酶抑制剂PTX和咯利普兰增强Aβ脑损伤大鼠学习记忆功能的机制之一。

AIM To investigate the effects of phosphodiesterase inhibitors on learning and memory impairment induced by amyloid β-protein （Aβ） and the possible underlying mechanisms. METHODS SD rats were randomly divided into 4 groups： sham operated group, model group, pentoxifylline （PTX, 16.5 mg·kg ^-1 ） grOUp and rolipram （ 1 mg·kg^- 1 ） grOUp. The rats in model and drug treatment groups were injected with Aβ25-35 5μL into each side of hippocampus. PTX or rolipram was given （ip） 24 h after the operation, once a day for 14 d. Step through test was done after administration for 7 d, and Morris water maze test was done after administration for 14 d. Hippocampal cAMP content was measured by radioimmunoassay after the behavior tests. RESULTS Compared with model group, the latency instep through test was significantly longer, and the time of finding platform in Morris water maze test was significantly shorter in PTX and rolipram groups, and the hippocampal cAMP content was higher. CONCLUSION Phosphodiesterase inhibitors PTX and rolipram may enhance learning and one of mechanisms may ing hippocampal cAMP memory abilities, and be related with increaslevel.