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.
出处
《中华神经外科杂志》
CSCD
北大核心
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）
