Department of Surgery, University of Bonn, Bonn, Germany.
Tytgat Institute of Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
Neurogastroenterol Motil. 2019 Mar;31(3):e13501. doi: 10.1111/nmo.13501. Epub 2018 Nov 8.
The cholinergic anti-inflammatory pathway comprises the perception of peripheral inflammation by afferent sensory neurons and reflex activation of efferent vagus nerve activity to regulate inflammation. Activation of this pathway was shown to reduce the inflammatory response and improve outcome of postoperative ileus (POI) and sepsis in rodents. Herein, we tested if a non-invasive auricular electrical transcutaneous vagus nerve stimulation (tVNS) affects inflammation in models of POI or endotoxemia.
Mice underwent tVNS or sham stimulation before and after induction of either POI by intestinal manipulation (IM) or endotoxemia by lipopolysaccharide administration. Some animals underwent a preoperative right cervical vagotomy. Neuronal activation of the solitary tract nucleus (NTS) and the dorsal motor nucleus of the vagus nerve (DMV) were analyzed by immunohistological detection of c-fos cells. Gene and protein expression of IL-6, MCP-1, IL-1β as well as leukocyte infiltration and gastrointestinal transit were analyzed at different time points after IM. IL-6, TNFα, and IL-1β serum levels were analyzed 3 hours after lipopolysaccharide administration.
tVNS activated the NTS and DMV and reduced intestinal cytokine expression, reduced leukocyte recruitment to the manipulated intestine segment, and improved gastrointestinal transit after IM. Endotoxemia-induced IL-6 and TNF-α release was also reduced by tVNS. The protective effects of tVNS on POI and endotoxemia were abrogated by vagotomy.
tVNS prevents intestinal and systemic inflammation. Activation of the DMV indicates an afferent to efferent central circuitry of the tVNS stimulation and the beneficial effects of tVNS depend on an intact vagus nerve. tVNS may become a non-invasive approach for treatment of POI.
胆碱能抗炎途径包括传入感觉神经元对周围炎症的感知以及传出迷走神经活动的反射激活，以调节炎症。该途径的激活被证明可以减少炎症反应，并改善术后肠梗阻（POI）和脓毒症的预后。在此，我们测试了非侵入性耳部经皮迷走神经刺激（tVNS）是否会影响 POI 或内毒素血症模型中的炎症。
在通过肠道操作（IM）诱导 POI 或脂多糖给药诱导内毒素血症后，小鼠接受 tVNS 或假刺激。一些动物接受术前右侧颈迷走神经切断术。通过免疫组织化学检测 c-fos 细胞分析孤束核（NTS）和迷走神经背核（DMV）的神经元激活。在 IM 后不同时间点分析白细胞介素 6（IL-6）、单核细胞趋化蛋白 1（MCP-1）、白细胞介素 1β（IL-1β）的基因和蛋白表达以及胃肠道转运。在给予脂多糖 3 小时后分析血清中 IL-6、TNFα 和 IL-1β 的水平。
tVNS 激活了 NTS 和 DMV，并减少了肠道细胞因子的表达，减少了白细胞向操作肠道段的募集，并改善了 IM 后的胃肠道转运。tVNS 还降低了内毒素血症诱导的 IL-6 和 TNF-α 的释放。tVNS 对 POI 和内毒素血症的保护作用被迷走神经切断术阻断。
tVNS 可预防肠道和全身炎症。DMV 的激活表明 tVNS 刺激的传入传出中枢回路，tVNS 的有益作用取决于完整的迷走神经。tVNS 可能成为治疗 POI 的一种非侵入性方法。
