长时程增强在幼年癫痫大鼠慢性认知功能障碍中的作用

Roles of Hippocampal long-term potentiation in chronic cognitive dysfunction of immature epileptic rats

目的 研究海马长时程增强(Long-term potentiation,LTP)在幼年癫痫大鼠慢性认知功能障碍中的作用.方法 新生SD大鼠出生后第21天随机分为生理盐水对照组和模型组,模型组大鼠腹腔注射氯化锂-匹罗卡品(Li-pilo),建立幼年癫痫大鼠模型.采用经Becker等修改后的Racine分级标准对癫痫大鼠癫痫发作行为进行观察评价,选择点燃出现RacineⅣ级以上并存活的大鼠进行实验.出生后第61 ~66天(P61~66)通过Morris水迷宫实验及旷场实验观察幼年癫痫大鼠成年后学习记忆功能(平均潜伏期、运动总路程)及自主探索行为(5min运动总路程).应用离体场电位的电生理学方法,观察比较模型大鼠与对照大鼠场电位LTP的变化,以探究海马LTP抑制是否参与癫痫大鼠慢性认知功能障碍形成.结果 ①水迷宫实验中,模型大鼠第5天平均潜伏期与对照大鼠比较显著增加(n=8,t=10.86,P<0.05),运动总路程显著延长(n=8,t=9.98,P<0.05);旷场实验中模型大鼠自主探索行为与对照大鼠相比明显减少(n=8,t=12.89,P<0.05).②模型大鼠海马基础场电位斜率与幅值与对照大鼠比较无明显改变,但高频刺激后斜率及幅值变化率与对照大鼠比较显著抑制(斜率:n=8,t=13.32,P<0.05;幅值:n=8,t=20.02,P<0.05).结论 幼年癫痫大鼠成年后出现认知功能障碍,海马LTP的减弱可能参与慢性认知功能障碍形成.

Objective To investigate the efects of hippocampal long-term potentiation(LTP)on cognitive dysfunction in inmature epileptie rats.Methods Immature epileptie rats were established by intraperitoneal injetion of lithium chloride-pilocarpine(l-pilo).Racine casification standard mdified by Becker was used to evaluate behavior of epileptic seizure,and the survival rats within Racine IV magnitude were selected in the experiment.The function of leaming and memory of epileptice rats when they were adult was asessed using Moris water maze experiment,and their independent exploratory behavior was evaluated by the open-field test.Field potential was recorded by electrophysiological tchnology to detecte whether hippocampal LTP was esential of cognitive dysfunction.Results The function of learming and memory was signfcanly impaired when compared with controls(n=8,t=10.86,P<0.05;n=8,t=9.98,P<0.05)..In ddition,independent exploratory behavior was sgificanly reduced when compared with controls(n=8,1=12.89,P<0.05).Besides,CA1 hippocampal LTP induced by high-frequency stimulation presented the significant inhibitin in epileptie rats with cognitive dysfunction when conpared with controls(Slope:n=8,l=13.32,P<0.05;Amplitude:n=8,t=20.02,P<0.05).Conclusion Inhibtion of CAI hippocampal LTP may be implicated in cognitive dysfunction of epileptic rats.