电刺激小脑顶核对脑梗死大鼠学习记忆能力及生长相关蛋白-43的影响

The effect of electrical stimulation of the cerebellar fastigial nucleus on learning, memory and the expression of growth-associated protein-43 after cerebral infarction

目的 观察电刺激小脑顶核（FNS）对脑缺血再灌注大鼠学习记忆能力及生长相关蛋白-43（GAP-43）表达的影响.方法 选用随机数字表法将60只健康成年雄性SD大鼠分为正常组、假手术组、FNS组及模型组,采用线栓法将FNS组及模型组大鼠制成左侧大脑中动脉栓塞/再灌注（MCAO/R）模型.FNS组大鼠于制模3h后给予FNS治疗,模型组仅将针电极置于大鼠小脑顶核部位,但不给予电刺激.分别于制模1d、3d及7d时采用Morris水迷宫实验检测各组大鼠学习记忆能力,并于上述时间点采用实时荧光定量PCR技术检测各组大鼠脑梗死部位GAP-43 mRNA表达.结果 制模后1d、3d及7d时模型组与FNS组大鼠Morris水迷宫逃避潜伏期均较正常组及假手术组明显延长（均P＜0.05）;FNS组大鼠上述时间点逃避潜伏期[分别为（25.72±0.42）s,（24.27±0.55）s和（23.82±0.63）s]则较模型组显著缩短（均P＜0.05）.在制模后1d、3d及7d时正常组与假手术组大鼠脑组织中仅存在少量GAP-43 mRNA表达;模型组及FNS组GAP-43mRNA表达在上述时间点均较正常组及假手术组显著增多（均P＜0.05）;并且上述时间点FNS组GAP-43mRNA表达[分别为（1.54±0.34）,（2.03±0.56）和（2.78±0.81）]亦显著强于模型组（均P＜0.05）.结论 FNS干预有助于改善脑缺血再灌注大鼠学习记忆能力,其治疗机制可能与上调脑梗死部位神经元GAP-43mRNA表达、从而促进脑梗死灶周围神经轴突再生及修复有关.

Objective To study the effect of electrical stimulation of the fastigial nucleus of the cerebellum （FNS） on learning,memory and the expression of growth-association protein-43 （GAP-43） after cerebral ischemia and reperfusion.Methods Sixty healthy,adult,male Sprague-Dawley rats were randomly divided into a normal group,a sham-operation group （sham group）,a model group and an FNS group,with 15 rats in each.Left middle cerebral artery occlusion and reperfusion （MCAO/R） was administered to the rats in the FNS and model groups using the thread embolism method.The rats of the FNS group were given FNS treatment using a pair of needle electrodes inserted into the cerebellar fastigial nucleus 3hrs after the MCAO/R.Needle electrodes were similarly inserted in the model group rats,but no electrical stimulus was applied.Then the rats＆#39; learning and memory abilities were tested using a Morris water maze on days 1,3 and 7 after the MCAO/R modeling.The expression of GAP-43 mRNA on the side of the cerebral infarction was detected using a quantitative,real-time polymerase chain reaction.Results The average escape]atencies of the rats in the model and FNS groups were significantly longer than those of the normal and sham groups at all time points,but the FNS group rats demonstrated a significantly shorter average escape latency than the rats of the model group at each time point.The normal and sham groups showed a significantly lower expression of GAP-43 mRNA than the model and FNS group rats at all time points.The FNS group rats had a significantly higher level of GAP-43 mRNA than the rats of the model group.Conclusion FNS improved the rats＇ learning and memory abilities.This might be associated with the up-regulation of GAP-43 mRNA in neurons on the side of the cerebral infarction which could promote the regeneration and repair of peripheral nerve axons in the area of the infarction.