刺激迷走神经对大鼠缺血性脑损伤保护作用的初步研究

Protective effect of vagus nerve stimulation on ischemic brain injury in rats: a preliminary study

目的探讨迷走神经刺激(VNS)对局灶性脑缺血模型大鼠的神经保护作用。方法成年雄性SD大鼠42只,根据体质量,采用计算机法将其随机分成假手术组(10只)、模型组(16只)、VNS治疗组(16只),每组又随机平均分为刺激左、右侧迷走神经亚组。采用线栓法建立大鼠局灶性脑缺血(2 h)-再灌注模型。造模后30 min,给予VNS治疗组大鼠颈部迷走神经刺激,刺激强度0.5mA,间期0.5ms,频率20Hz,在1h内每隔5min刺激1次,每次持续30s。不给予模型组大鼠刺激,对假手术组大鼠既不栓塞血管也不刺激神经。操作过程中监测损伤侧脑体感诱发电位(SEP,包括N1波幅和P1潜伏期)的变化;造模前5min开始,造模后150min结束。造模后24h行神经行为学评分,处死大鼠,测定脑梗死体积。结果 (1)在刺激左侧迷走神经的大鼠中,假手术组、模型组及VNS治疗组的神经行为学评分分别为(0.4±0.2)、(9.5±0.4)及(6.4±0.3)分;在刺激右侧迷走神经的大鼠中,3组的神经行为学评分分别为(0.6±0.2)、(9.3±0.4)和(6.9±0.4)分。模型组的评分与其他两组比较,差异有统计学意义(P<0.05)。(2)与模型组相比,VNS治疗组的脑梗死体积减少[刺激左侧迷走神经分别为(120±7)、(56±7)mm3;刺激右侧迷走神经分别为(115±10)、(54±8)mm3],差异有统计学意义(P<0.05)。(3)与假手术组和VNS组比较,模型组的SEP波形中的N1波幅下降、P1潜伏期延长,差异有统计学意义(P值均<0.05);(4)VNS治疗组中刺激左、右侧迷走神经,在脑梗死体积、神经行为学评分、SEP波形中的N1波幅和P1潜伏期上差异均无统计学意义(P>0.05)。结论无论是刺激左侧还是右侧迷走神经,对缺血性脑损伤都具有神经保护作用,且在作用效果上无明显差别。

Objective To investigate the neuroprotective effect of vagus nerve stimulation （ VNS） on a model rat of focal cerebral ischemia. Methods A total of 42 adult male Sprague-Dawle （ SD） rats were randomly divided into a sham operation group （n=10）,a model group （n=16）,and a VNS-treated group （ n = 16 ） . Each group was randomly redivided into 2 subgroups：left VNS subgroup and right VNS subgroup. A model of focal cerebral ischemia （2 h） in rats was induced by the intraluminal suture method. At 30 minutes after modeling, the VNS-treated group received cervical VNS, the stimulation intensity was 0. 5 mA,the interval was 0. 5 ms,and the frequency was 20 Hz. Stimulation was once every 5 min within 1 h and each lasted for 30 s. The model group did not give any stimulation. Neither blood vessels were embolized nor were the nerves stimulated in the sham operation group. The changes of somatosensory evoked potentials （ SEP） on the lesion sides during operation were monitored. At 24 h after modeling,the neurobehavioral scores were performed. The rats were sacrificed,and their brain infarct volume was measured. Results （1） During＆amp;nbsp;the stimulation of left VNS in rats,the neurobehavioral scores of the sham operation group,model group and VNS-treated group were 0. 4 ± 0. 2,9. 5 ± 0. 4,6. 4 ± 0. 3,respectively;during the stimulation of right VNS in rats,the neurobehavioral scores of the 3 groups were 0. 6 ± 0. 2,9. 3 ± 0. 4,and 6. 9 ± 0. 4,respectively. There were significant differences between the scores of the model group and those of the other 2 groups （P〈0. 05）. （2） Compared with the model group,the brain infarct volume of the VNS-treated group was reduced （ stimulating the left VNS of the 2 groups was 120 ± 7 and 56 ± 7 mm3 respectively;stimulating the right VNS was 115 ± 10 and 54 ± 8 mm3 respectively ） . There were significant differences （ P 〈0. 05）. （3） Compared with the sham operation group and the VNS-treated group,the SEP N1 amplitude of the model group was decreased significantly and the P1 latency was prolonged significantly. There was significant difference （P〈0. 05）. （4） There were no significant differences in the stimulation of the left or right VNS in the VNS-treated group among the infarct volume, neurobehavioral scores, SEP amplitude,and latency （P〉0. 05）. Conclusion No matter whether to stimulate the left or right vagus nerves, they both have neuroprotective effects on ischemic brain injury, and there was no significant difference on the action effects.