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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 investigate the effect of percutaneous (Alopecia) vagus nerve stimulation (ta-VNS) and vagus nerve stimulation (VNS) on the treatment of epileptic seizures in drug-refractory epileptic rats. Methods Temporal lobe epilepsy rats were induced by lithium chloride-pilocarpine, and induced by phenobarbital sodium (PB). On this basis, the rats were randomly divided into blank control group (normal saline instead of pilocarpine), RE group (no stimulation treatment), RE + ta-VNS group (percutaneous vagal nerve stimulation ), RE + false ta-VNS group (the electrode pads were placed in the cavum but not electrified), RE + VNS group (vagus nerve stimulation) and RE + false VNS group (implanted vagus nerve stimulation electrode but not electrified). Four weeks after the stimulation, the frequency of seizures in each group was compared. The hippocampal slices were taken from the decapitated rats. Nissl and TUNEL staining were used to observe the morphological changes and apoptosis of hippocampal neurons in each group. Results The average seizure frequency of 1 RE + ta-VNS group and RE + VNS group decreased by 72.0% and 80.7%, respectively, which were significantly different from that of RE group (P <0.05) (P = 0.12). There was no significant difference between RE + false ta-VNS group, RE + false VNS group and RE group. The Nissl and TUNEL staining showed that the hippocampal neurons in RE group, RE + false ta-VNS group and RE + Falcon VNS group were severely damaged compared with the blank control group, and the lesions in RE + ta-VNS group and RE + VNS group were less severe, The difference between RE + ta-VNS group and RE + VNS group was not statistically significant. Conclusion Both ta-VNS and VNS can significantly reduce the number of epileptic seizures in RE rats and reduce the damage of hippocampal neurons, both of which are close to each other. However, ta-VNS has the advantages of noninvasiveness and few side effects.