迷走神经刺激对药物难治性癫痫大鼠脑内多药耐药蛋白过表达的抑制作用  

The inhibitory effects of vagus nerve stimulation in drug refractory epilepsy rat brains on the overexpression of the multidrug resistance protein

作　　者：张元杰[1] 徐纪文[1] 田鑫[1] 王桂松[1] 周洪语[1] 李骁雄[1] 赵晨杰[1] 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,200127

出　　处：《中华神经外科杂志》2013年第1期30-34,共5页Chinese Journal of Neurosurgery

基　　金：上海市科委基础研究重点项目（编号：10JC1409700）

摘　　要：目的主要研究迷走神经刺激（VNS）对癫痫大鼠脑内多药耐药蛋白（P-gP）表达的调控作用。方法采用氯化锂-匹鲁卡品制备颞叶癫痫大鼠，苯巴比妥钠（PB）诱导建立药物难治性癫痫（RE）大鼠模型。在此模型基础上，大鼠按随机数字表顺序分为四组：单纯VNS（A）组、VNS＋PB（B）组、假VNS＋PB（C）组、生理盐水（D）组。VNS组行刺激电极植入术，通过改进的VNS参数（频率30H2，波宽500μs，电流0．75mA，刺激时间30s，间歇5min，12h／d）进行电刺激，观察各组大鼠VNS前后发作次数，检测各组P-gP表达含量的变化。结果（1）A、B组癫痫平均发作次数分别减少79．6％和85．9％，C、D组无明显改善；（2）B组P-gP过表达量与C组相比差异有统计学意义（P〈0．05），A组P-gP表达量较D组差异有统计学意义（P〈0．05）。结论VNS疗法可以有效降低RE的发作次数，对由药物引起的P-gP的过表达具有较强的抑制作用，与药物联合应用可以达到较好的治疗效果。Objective To study the role of vagus nerve stimulation in the regulating of muhidrug resistance genes related to protein （P- glyeoprotein ） overexpression in rat brains with drug refractory epilepsy （mainly refers to the hippoeampus and the piriform cortex）. Methods Lithium -Pilocarpine was used to kindle the rats to establish the temporal lobe epilepsy model and then rat models were induced with drug- refractory epilepsy by Sodium phenobarbital （PB）. The rats were randomly divided into 4 groups, and then implanted with VNS electrodes. Modified parameters were used in the procedure of VNS （ frequency -30Hz, pluse width - 0. 5ms, current - 0. 5 mA, stimulation time - 30 s, interval - 5 min, 12h/d）. Fluctuations in epileptic seizure frequencies were observed, and the amount of P - gp overexpression was detected before and after four weeks in each treatment group. Results （ 1 ） The VNS and VNS ＋ PB groups had a 79. 6% and 85.9% decrease in the average number of seizures. The sham VNS ＋ PB and saline groups had no significant improvements ; （2） The expression of P - gp levels in the VNS ＋ PB group had significant statistical differences compared with the sham VNS ＋ PB group （P 〈 0.05 ） . Conclusion VNS can effectively reduce the frequency of seizures of the RE, and it has a strong inhibitory effect on the overexpression of the multidrug resistance protein （ P - gp） o Furthermore, better therapeutic effect can be achieved with this drug combination.

关 键 词：难治性耐药性癫痫 迷走神经刺激 多药耐药基因 P-糖蛋白 癫痫持续 状态 

分 类 号：R742.1[医药卫生—神经病学与精神病学]