经皮迷走神经耳支刺激与迷走神经刺激对药物难治性癫痫大鼠治疗效果的比较  

The comparison between the antiepileptic effects of transcutaneous auricular vagus nerve stimulation and vagus nerve stimulationin in drug refractory epileptic rats

作　　者：杨佃旭 王桂松[1] 王丽丽[1] 徐志明[1] 杨建[1] 葛建伟[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,上海200127

出　　处：《立体定向和功能性神经外科杂志》2015年第5期261-265,共5页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：上海市科委生物医药支撑计划项目(编号:13441903000)

摘　　要：目的探讨经皮(耳甲腔)迷走神经耳支电刺激(ta-VNS)与迷走神经电刺激(VNS)对药物难治性癫痫(RE)大鼠癫痫发作治疗效果的差异。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)诱导筛选RE大鼠模型。在此基础上,将大鼠随机分为空白对照组(建模时用生理盐水代替匹鲁卡品)、RE组(不做刺激处理)、RE+ta-VNS组(经皮迷走神经耳支刺激)、RE+假ta-VNS组(耳甲腔处安置电极片但不通电)、RE+VNS组(迷走神经刺激)和RE+假VNS组(植入迷走神经刺激电极但不通电)。4周刺激结束后比较各组大鼠发作频率,断头取脑制作海马切片行Nissl和TUNEL染色观察各组海马神经元的形态学变化和损伤凋亡情况。结果 1 RE+ta-VNS组和RE+VNS组癫痫平均发作频率分别减少72.0%和80.7%,均与RE组有显著性差异(P<0.05),RE+ta-VNS组和RE+VNS组之间差异无统计学意义(P=0.12),RE+假ta-VNS组、RE+假VNS组和RE组间无统计学差异。2 Nissl和TUNEL染色显示:与空白对照组相比RE组、RE+假ta-VNS组和RE+假VNS组大鼠海马神经元损伤严重,RE+ta-VNS组和RE+VNS组损伤较轻,RE+ta-VNS组和RE+VNS组之间差异无统计学意义。结论 ta-VNS和VNS均可显著低RE大鼠的癫痫发作次数、减轻海马神经元的损伤,两者的效果接近,但是ta-VNS具有无创性、副作用少等优点。Objective To study the difference between the therapeutic effects of transcutaneous auricular vagus nerve stimulation and vagus nerve stimulation on seizures in drug refractory epileptic rat models.Methods Lithium chloride-Pilocarpine was used to establish rat models of spontaneous recurrent temporal lobe epilepsy,and then the drug refractory epileptic rats were screened out by Sodium Phenobarbital.The rats were randomly divided into six groups.The frequency of seizures was compared after the stimulation of 4weeks.The pathological changes and apoptosis of hippocampal neurons were studied by Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL）technology.Results ①The RE＋ta-VNS and RE＋ VNS groups had a 72.0% and 80.7% decrease in the average frequency of seizures,and there were statistical differences between the two groups and the RE group（P〈0.05）.But there was no statistical difference between the RE＋ta-VNS and RE＋ VNS groups（P=0.12）.There were no statistical differences among the RE,RE＋ sham ta-VNS and RE＋sham VNS groups.②Nissl and TUNEL staining showed that the neuronal injury and apoptosis in hippocamp of the RE,RE＋ sham ta-VNS and RE＋ sham VNS groups were more serious than those of the blank control group.And those of the RE＋ ta-VNS and RE＋ VNS groups were lighter.Conclusion Both ta-VNS and VNS not only can reduce the frequency of seizures significantly but also can protect hippocampal neurons effectively in drug refractory epileptic rats.The effects of ta-VNS are near to those of VNS,but ta-VNS has the advantages of noninvasion,less side effects and so on.

关 键 词：药物难治性癫痫 大鼠 经皮迷走神经耳支刺激 迷走神经刺激 

分 类 号：R742.1[医药卫生—神经病学与精神病学]