迷走神经电刺激对难治性癫痫大鼠模型脑电图的影响

Establishment of animal model of refractory epilepsy and preliminary study of the effects of vagus nerve stimulation on electroencephalogram in this model

目的建立难治『生癫痫（refractary epilepsy，RE）大鼠模型，并研究迷走神经刺激（VNS）对其脑电图的影响。方法在氯化锂一匹鲁卡品诱导的颞叶癫痫（temple lobe epilepsy，TIE）大鼠模型基础上，用苯巴比妥钠（PB）进行诱导并筛选出耐药大鼠。将耐药大鼠分成三组，分别为VNS组（进行迷走神经刺激）、假VNS组（植入迷走神经刺激电极但不通电刺激）、EP对照组（不做处理）。对大鼠植入迷走神经刺激电极和脑电图记录电极，然后用视频脑电系统进行同步监控。比较迷走神经刺激前与刺激4周后癫痫发作相关指标的变化。结果（1）视频记录结果显示，迷走神经刺激后的大鼠癫痫平均发作次数较刺激前显著减少（P〈0．05）；其余两组未见明显变化；（2）脑电图结果显示，迷走神经刺激后的大鼠各项指标（包括每次癫痫发作的平均持续时间、癫痫发作时每秒出现的尖棘波的数目、癫痫发作过程中相邻两个尖棘波在相同时间间隔的个数）较迷走神经刺激前也有统计学意义上的显著性减少（P〈0．05）；其余两组未见明显变化；（3）脑电信号时间频率图显示，迷走神经刺激后癫痫大鼠脑电频率比刺激前降低，能量峰值未见明显变化，但峰值明显高于同龄正常大鼠。结论（1）在氯化锂-匹鲁卡品诱导的TEE大鼠模型基础上，用PR可以诱导出药物难治『生癫痫模型。（2）迷走神经刺激术能够降低该难治性癫痫模型的癫痫发作次数，尤其是改变其脑电发作模式，这或许是VNS治疗癫痫的的机制之一。

Objective To establish the refractory epilepsy （RE） rat model and study the effects of vagus nerve stimulation on electroencephalogram （EEG） in RE rats. Methods Based on the Lithium -Pilocarpine induced temporal lobe epilepsy model, screening out the anti - PB epileptic rats by Sodium Phenobarbital （PB） . The rats were randomly divided into 3 groups ： VNS group, sham - VNS group and control group. The parameters of the VNS were set as follows： frequency 30 Hz , pluse width 0. 5 ms , current 1 mA ,stimulation time 30s , interval 5 min , 10 hours/day . Behavior and EEG were observed by Video - EEG systerm before and after four - week VNS in each group. Results （ 1 ） The frequency of seizures in VNS group was significantly reduced after 4 - week VNS （ P 〈 0.05 ） , but that of group sham - VNS and group control did not change significantly. （2） The indexs of group VNS, including the duration of seizures, the spike numbers and spike interval, were significantly reduced after 4 - week VNS （ P 〈 0.05 ） , however the sham -VNS and EP control groups did not change significantly. （3）The spectrogram showed epileptiform - wave frequency of epileptic rat reduced after 4 - week VNS, but the maximum energy value did not change obviously, though it was higher than that of normal rats with the same age. Conclusions The RE rat could be screened out by PB on the basis of TLE epilepsy model. VNS could efficiently decrease the frequency of seizures, especially change the EEG pattern.