程怡慧,段昱,夏晓昧,等.迷走神经刺激对小鼠脑缺血再灌注损伤的神经保护作用研究[J].中华物理医学与康复杂志,2026,48(5):390-399
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| 迷走神经刺激对小鼠脑缺血再灌注损伤的神经保护作用研究 |
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| DOI：10.3760/cma.j.cn421666-20250423-00361 |
| 中文关键词: 迷走神经刺激 缺血再灌注损伤 自噬 凋亡 神经保护作用 |
| 英文关键词: Vagus nerve stimulation Ischemia-reperfusion injury Autophagy Apoptosis Neuroprotective effects |
| 基金项目:国家自然科学基金资助项目（82472597） |
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| 中文摘要: |
| 目的 研究急性脑缺血/再灌注（I/R）损伤后迷走神经刺激（VNS）干预时机，比较侵入式迷走神经刺激（iVNS）与经皮耳迷走神经刺激（taVNS）的神经保护作用，并探索taVNS的作用机制和长期疗效。 方法 采用小鼠短暂性大脑中动脉栓塞（tMCAO）模型，按照随机数字表法进行分组，每组10只。研究分三部分：首先，在缺血时或再灌注后行iVNS干预，24 h后评估神经功能、脑梗死体积及脑含水量；其次，再灌注后行iVNS和taVNS干预，24 h后评估不同干预对大鼠神经功能、脑梗死体积及脑含水量的影响，并检测缺血半暗带中凋亡与自噬相关蛋白的表达水平；最后，连续taVNS干预14 d，分别于第1、4、7、14 天评估神经功能、脑梗死体积及上肢功能，评估长期疗效。假手术组和未治疗模型组用作对照组。 结果 缺血时和再灌注后iVNS干预组的神经功能、脑梗死体积和脑含水量均显著改善（P<0.05），但2组组间无显著差异；再灌注后taVNS组的神经功能、脑梗死体积和脑含水量均显著改善（P＜0.05），但和再灌注后iVNS比较，脑梗死体积和脑含水量无显著差异（P＞0.05）；taVNS可显著改善脑卒中后神经功能，显著下调Bax、cleaved caspase-3、Map1lc3b-Ⅱ/Ⅰ和Becn1表达水平，并上调Bcl-2与Sqstm1/p62表达水平（P<0.05）；taVNS干预对神经功能、脑梗死体积及上肢功能改善呈时间累积效应，在第14天效果最佳（P<0.05），且上肢功能恢复接近假手术组水平（P>0.05）。 结论 缺血时和再灌注后不同时间点iVNS干预疗效相当；iVNS和taVNS均可减轻急性脑I/R的神经损伤，taVNS通过抑制凋亡和自噬发挥神经保护作用。taVNS连续干预具有累积效应，可显著促进小鼠上肢运动及感觉功能恢复。 |
| 英文摘要: |
| Objective To investigate the optimal timing of vagus nerve stimulation (VNS) in treating cerebral ischemia-reperfusion (I/R) injuries and to compare the neuroprotective effects of invasive VNS (iVNS) with those of transcutaneous auricular VNS (taVNS), exploring the underlying mechanisms and the long-term effectiveness of taVNS. Methods Transient middle cerebral artery occlusion (tMCAO) was modeled in mice，which were then randomly assigned to different groups using a random number table, with 10 mice in each group. iVNS was then applied during ischemia or after reperfusion, and neurological function, cerebral infarct volume, and brain water content were assessed 24h later. Subsequently, iVNS or taVNS was administered and neurological function, infarct volume, and brain water content were again evaluated after 24h. The levels of apoptosis- and autophagy-related proteins in the ischemic penumbra were also measured. In a third phase, taVNS was administered daily for 14 consecutive days, and neurological function, infarct volume, and forelimb function were assessed on days 1, 4, 7 and 14 to evaluate long-term efficacy. The sham group and the untreated model group served as control groups. Results iVNS applied either during ischemia or after reperfusion significantly improved neurological function and reduced the cerebral infarct volume and brain water content. There was no significant difference in their effectiveness. After reperfusion, neurological function, cerebral infarct volume, and brain water content were significantly improved in the taVNS group. However, compared with the iVNS group after reperfusion, there were no significant differences in cerebral infarct volume or brain water content. taVNS significantly improved post-stroke neurological function, and it also significantly downregulated Bax, cleaved caspase-3, Map1lc3b-II/I, and Becn1, and significantly upregulated Bcl-2 and Sqstm1/p62. The greatest effects of taVNS on neurological function, infarct volume, and forelimb function were observed on day 14, when the average forelimb function had recovered to a level comparable to that of the sham group. Conclusion iVNS exerts comparable neuroprotective effects against acute cerebral I/R injury when it is applied during ischemia or after reperfusion. taVNS alleviates neurological injury following acute cerebral I/R injury and exerts neuroprotective effects through by inhibiting apoptosis and autophagy. Longer term, taVNS produces cumulative effects and significantly promotes the recovery of forelimb motor function and sensation in mice. |
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