期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 163, 期 5, 页码 1007-1016出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1476-5381.2011.01296.x
关键词
post-operative ileus; intestinal muscle inflammation; cholinergic anti-inflammatory pathway; semapimod; intracerebroventricular; dorsal motor nucleus; paraventricular nucleus; macrophages; mice
资金
- Technology Foundation STW
- ministry of Economic Affairs (NWO-STW) [AKG.5727]
- Netherlands Organisation for Scientific Research (NWO)
- Flemish 'Fonds Wetenschappelijk Onderzoek' (FWO) [G.0905.07]
BACKGROUND AND PURPOSE Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. EXPERIMENTAL APPROACH Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 mu g center dot kg-1) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. KEY RESULTS Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. CONCLUSIONS AND IMPLICATIONS Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据