脑内5-羟色胺减少对致痫大鼠癫痫发作及学习记忆的影响

Effect of serotonin depletion on seizures learning-memory in pilocarpine-induced epileptic rats

目的:于中脑正中中缝核局部微量注射5,7-二羟色胺(5,7-DHT),探讨5-羟色胺(5-HT)与癫痫的关系及匹罗卡品(PILO)致痫大鼠学习记忆改变的可能机制。方法:成年SD大鼠随机分为PILO组、PILO+5,7-DHT组、空白对照组三组,然后根据是否出现癫痫持续状态(SE)再将PILO组分成:PILO+SE组和PILO-SE组两亚组;利用视频脑电图观察大鼠癫痫发作及皮层脑电变化;运用Morris水迷宫测评大鼠空间学习记忆水平;最后运用免疫组化法观察大鼠中缝核5-HT能神经元。结果:大鼠予以5,7-DHT(PILO+5,7-DHT组)处理后造模成功率、死亡率及慢性期自发性发作频率均增高;与空白组比较PILO+SE组中缝核5-HT能神经元数目有所下降(P<0.05),而PILO+5,7-DHT组下降更明显(P<0.01);与空白组比较PILO+SE组平均逃避潜伏期延长、穿越平台次数减少、原平台象限停留时间缩短(P<0.05),而与PILO+SE组比较PILO+5,7-DHT组变化不明显。结论:脑内5-HT水平的降低容易诱发癫痫发作,尚不能认为癫痫大鼠合并认知功能障碍与脑内5-HT水平下降有关。

Objective： To investigate the relationship between semtonin（5-HT）and epilepsy and the mechanism of learning-memory in pi- locarpine（PILD）-induced epileptic rats after 5,7-dihydroxytryptamine （5,7-DHT） microinjection in median raphe nucleus. Methods： Adult S D rats were randomly divided into 3 groups： PILO group, PILO＋ 5,7-DHT group, vehicle control group; PILO group was divided into two groups by status epilepticus（SE）： PILO ＋ SE group and PILO-SE group. The rats＇ seizures and cortex electroencephalography（EEG） were ob- served by vedio EEG. The rats＇ spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic neuron in raphe nuclei was observed by immunohistochemisty. Results： After treatment of 5,7-DHT （PILO ＋ 5,7-DHT group）, the success rate, the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved. Compared with the control group, the num- ber of serotonergic neuron in raphe nuclei was decrease in PILO ＋ SE group（ P 〈 0.05）. Moreover, it＇s extremely decrease in PILO ~ 5,7- DHT group（ P 〈 0.01） ： Compared with control group, the mean escape latency was prolonged, the times of crossing target was decreased and the retention time in target zone was shortened in PILO ＋ SE group（ P 〈 0.05）, but there was no significant difference between PIID ＋ SE group and PILO ＋ 5,7-DHT group. Condusion： Depletion of serotonin may facility the rats＇ epileptic seizures, but we could not interpret which may cause epileptic rats＇ cognitive deficit.