Department of Radiology, Grosshadern Clinic, Ludwig-Maximilians-University Munich, Munich, Germany.
Center for Human Genetics and Laboratory Diagnostics, Medical Labs Martinsried, Martinsried, Germany.
Neurogastroenterol Motil. 2022 Feb;34(2):e14308. doi: 10.1111/nmo.14308. Epub 2021 Dec 27.
BACKGROUND: Postoperative ileus (POI) involves an intestinal inflammatory response that is modulated by afferent and efferent vagal activation. We aimed to identify the potential influence of the vagus nerve on POI by tracking central vagal activation and its role for peripheral inflammatory changes during the early hours after surgery. METHODS: C57BL6 mice were vagotomized (V) 3-4 days prior to experiments, while control animals received sham vagotomy (SV). Subgroups underwent either laparotomy (sham operation; S-POI) or laparotomy followed by standardized small bowel manipulation to induce postoperative ileus (POI). Three hours and 9 h later, respectively, a jejunal segment was harvested and infiltration of inflammatory cells in intestinal muscularis was evaluated by fluorescein isothiocyanate (FITC) avidin and myeloperoxidase (MPO) staining. Moreover, the brain stem was harvested, and central nervous activation was investigated by Fos immunochemistry in both the nucleus of the solitary tract (NTS) and the area postrema (AP). Data are presented as mean ± SEM, and a p < 0.05 was considered statistically significant. KEY RESULTS: Three hour experiments revealed no significant differences between all experimental groups, except MPO staining: 3 h after abdominal surgery, there were significantly more MPO-positive cells in vagotomized S-POI animals compared to sham-vagotomized S-POI animals (26.7 ± 7.1 vs. 5.1 ± 2.4, p < 0.01). Nine hour postoperatively intramuscular mast cells (IMMC) were significantly decreased in the intestinal muscularis of V/POI animals compared to SV/POI animals (1.5 ± 0.3 vs. 5.9 ± 0.2, p < 0.05), while MPO-positive cells were increased in V/POI animals compared to SV/POI animals (713.2 ± 99.4 vs. 46.9 ± 5.8, p < 0.05). There were less Fos-positive cells in the NTS of V/POI animals compared to SV/POI animals (64.7 ± 7.8 vs. 132.8 ± 23.9, p < 0.05) and more Fos-positive cells in the AP of V/POI animals compared to SV/POI animals 9 h postoperatively (38.0 ± 2.0 vs. 13.7 ± 0.9, p < 0.001). CONCLUSIONS AND INTERFERENCES: Afferent nerve signaling to the central nervous system during the development of early POI seems to be mediated mainly via the vagus nerve and to a lesser degree via systemic circulation. During the early hours of POI, the intestinal immune response may be attenuated by vagal modulation, suggesting interactions between the central nervous system and the intestine.
背景：术后肠麻痹（POI）涉及肠道炎症反应，其受传入和传出迷走神经激活的调节。我们旨在通过跟踪中枢迷走神经激活及其在外周炎症变化中的作用，来确定迷走神经对 POI 的潜在影响。
方法：C57BL6 小鼠在实验前 3-4 天接受迷走神经切断术（V），而对照动物则接受假手术迷走神经切断术（SV）。部分动物接受剖腹术（假手术；S-POI）或剖腹术加标准化小肠操作，以诱导术后肠麻痹（POI）。分别在 3 小时和 9 小时后，取出一段空肠，通过荧光素异硫氰酸酯（FITC）亲和素和髓过氧化物酶（MPO）染色评估肠道肌层的炎症细胞浸润。此外，还取出脑干，通过 Fos 免疫组织化学法在孤束核（NTS）和后极（AP）中研究中枢神经激活。数据以平均值±SEM 表示，p<0.05 被认为具有统计学意义。
主要结果：3 小时的实验结果显示，除 MPO 染色外，所有实验组之间均无显著差异：术后 3 小时，迷走神经切断的 S-POI 动物的 MPO 阳性细胞明显多于假手术迷走神经切断的 S-POI 动物（26.7±7.1 比 5.1±2.4，p<0.01）。术后 9 小时，V/POI 动物的肠道肌层中的肌间肥大细胞（IMMC）明显减少，而 V/POI 动物的 MPO 阳性细胞增加（1.5±0.3 比 5.9±0.2，p<0.05）。V/POI 动物的 NTS 中 Fos 阳性细胞较 SV/POI 动物减少（64.7±7.8 比 132.8±23.9，p<0.05），而 V/POI 动物的 AP 中 Fos 阳性细胞较 SV/POI 动物增加（38.0±2.0 比 13.7±0.9，p<0.001）。
结论和干扰：在早期 POI 发展过程中，传入神经向中枢神经系统的信号似乎主要通过迷走神经传递，而通过全身循环传递的程度较小。在 POI 的早期阶段，肠道免疫反应可能通过迷走神经调节而减弱，这表明中枢神经系统和肠道之间存在相互作用。
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