Vagus nerve integrity and experimental colitis
Vagus nerve integrity and experimental colitis
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DOI：
10.1152/ajpgi.00098.2007
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发表时间：
2007-09-01
影响因子：
4.5
通讯作者：
Collins, Stephen M.
中科院分区：
文献类型：
--
作者：
Ghia, Jean-Eric;Blennerhassett, Patricia;Collins, Stephen M.
先前的研究已经确定了内毒素休克背景下的抗炎迷走神经反射。我们已经扩展了这一观察结果，以表明迷走神经对葡聚糖硫酸钠（DSS）或二硝基苯磺酸（DNBS）诱导的急性（5天）结肠炎具有保护作用。我们已经表明，这是通过巨噬细胞介导的，并涉及抑制促炎细胞因子。在这项研究中，我们通过研究在迷走神经切断术后9至61天DNBS和DSS诱导的结肠炎症反应来检查迷走神经的完整性是否赋予持久的保护。在所有时间点使用CCK诱导的饱腹感证实迷走神经切断术的完整性。如先前在DNBS和DSS模型中所述，与幽门成形术相关的迷走神经切断术增加了所有炎症指数。迷走神经切断术使疾病活动指数以及宏观和组织学评分分别增加75%和41%。此外，当迷走神经切断术后9天诱导结肠炎时，髓过氧化物酶（MPO）活性、血清C反应蛋白（CRP）水平和结肠组织促炎细胞因子水平升高。然而，在迷走神经切断术后21、33和61天诱导的结肠炎小鼠中，这些炎症指数的增加基本上减少。这伴随着白细胞介素-10、转化生长因子-β、结肠组织中叉头盒P3（FOXP 3）染色和血清皮质酮的产生增加。这些发现表明，尽管迷走神经完整性是一个重要的保护因素，但如果迷走神经完整性受损超过2周，其他抗炎机制也会发挥作用。
Previous studies have identified a counterinflammatory vagal reflex in the context of endotoxic shock. We have extended this observation to show that the vagus confers protection against acute ( 5 days) colitis induced by dextran sodium sulfate ( DSS) or by dinitrobenzene sulfonic acid ( DNBS). We have shown that this is mediated via macrophages and involves the suppression of proinflammatory cytokines. In this study, we have examined whether the vagal integrity confers long- lasting protection by studying DNBS- and DSS- induced inflammatory responses in the colon at 9 to 61 days postvagotomy. The integrity of vagotomy was confirmed at all time points using CCK- induced satiety. As previously described in a DNBS and DSS model, vagotomy associated with the pyloroplasty increased all indices of inflammation. Vagotomy increased the disease activity index as well as the macroscopic and histological scores by 75 and 41%, respectively. In addition, myeloperoxidase ( MPO) activity, serum levels of C- reactive protein ( CRP), and colonic tissue levels of proinflammatory cytokine increased when colitis was induced 9 days postvagotomy. However, these increases in inflammatory indices were substantially diminished in mice with colitis induced 21, 33, and 61 days postvagotomy. This was accompanied by an increased production of interleukin- 10, transforming growth factor- beta, Forkhead Box P3 ( FOXP3) staining in colonic tissue, and serum corticosterone. These findings indicate that although vagal integrity is an important protective factor, other counterinflammatory mechanisms come into play if vagal integrity is compromised beyond 2 wk.