CAJ | 학술논문

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30 Hz,波宽500μs,电流0.75 mA,刺激时间30 s,间歇5min,12 h/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.
목적 주요연구미주신경자격(VNS)대전간대서뇌내다약내약단백(P-gp)표체적조공작용.방법 채용록화리-필로잡품제비섭협전간대서,분파비타납(PB)유도건립약물난치성전간(RE)대서모형.재차모형기출상,대서안수궤수자표순서분위사조:단순VNS(A)조、VNS+ PB(B)조、가VNS+PB(C)조、생리염수(D)조.VNS조행자격전겁식입술,통과개진적VNS삼수(빈솔30 Hz,파관500μs,전류0.75 mA,자격시간30 s,간헐5min,12 h/d)진행전자격,관찰각조대서VNS전후발작차수,검측각조P-gp표체함량적변화.결과 (1)A、B조전간평균발작차수분별감소79.6％화85.9％,C、D조무명현개선；(2)B조P-gp과표체량여C조상비차이유통계학의의(P＜0.05),A조P-gp표체량교D조차이유통계학의의(P＜0.05).결론 VNS요법가이유효강저RE적발작차수,대유약물인기적P-gp적과표체구유교강적억제작용,여약물연합응용가이체도교호적치료효과.
Objective To study the role of vagus nerve stimulation in the regulating of multidrug resistance genes related to protein (P-glycoprotein) overexpression in rat brains with drug refractory epilepsy (mainly refers to the hippocampus 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 + PBgroups 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.