The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice
The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice
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DOI：
10.1053/j.gastro.2006.02.022
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发表时间：
2006-05-01
期刊：
影响因子：
29.4
通讯作者：
Van der Poll, T.
中科院分区：
文献类型：
--
作者：
Van Westerloo, David J.;Giebelen, Ilona A.;Van der Poll, T.
背景与目的：神经系统通过迷走神经，通过减少内毒素刺激的巨噬细胞释放肿瘤坏死因子- α来控制炎症。这种抗炎作用是由迷走神经的主要神经递质乙酰胆碱与巨噬细胞表达α 7亚基的胆碱能烟碱受体相互作用介导的。方法：为了确定这种“烟碱抗炎途径”在实验性胰腺炎中的作用，我们通过12小时腹腔注射蓝蛋白诱导小鼠胰腺炎。胰腺炎前行单侧左颈迷走神经切除术或用烟碱受体拮抗剂甲美胺或选择性α - 7烟碱受体激动剂3-（2,4-二甲氧基苄基）皂素（ISTS-21）预处理。结果：迷走神经切开术或甲美胺预处理导致胰腺炎的严重程度增加，这反映在组织学、水肿、血浆水解酶和白细胞介素-6水平上。此外，骨髓过氧化物酶含量和胰腺内中性粒细胞染色显示，这些小鼠迁移到胰腺的中性粒细胞数量增加。相反，GTS-21预处理能显著降低胰腺炎的严重程度。胰腺炎相关的肺部炎症与迷走神经和烟碱受体的完整性无关。结论：本研究首次证明迷走神经和“烟碱抗炎途径”在减轻实验性胰腺炎的炎症和损伤方面具有治疗潜力。
Background & Aims: The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-alpha from endotoxin stimulated macrophages. This anti-inflammatory effect is mediated by an interaction of acetylcholine, the principal neurotransmitter of the vagus nerve, with macrophage cholinergic nicotinic receptors expressing the alpha 7 subunit. Methods: To determine the role of this "nicotinic anti-inflammatory pathway" in experimental pancreatitis, we induced pancreatitis in mice by 12 hourly intraperitoneal injections of cerulein. Pancreatitis was preceded by unilateral left cervical vagotomy or pretreatment with the nicotinic receptor antagonist mecamylamine or by pretreatment with the selective alpha 7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (ISTS-21). Results: Vagotomy or pretreatment with mecamylamine resulted in an enhanced severity of pancreatitis, as reflected by histology, edema, plasma hydrolases, and interleukin-6 levels. Furthermore, the number of neutrophils migrated to the pancreas was increased in these mice, as shown by myeloperoxiclase content and intrapancreatic staining of neutrophils. Conversely, GTS-21 pretreatment strongly decreased the severity of pancreatitis. Pancreatitis-associated pulmonary inflammation was independent of the integrity of the vagus nerve and nicotinic receptors. Conclusions: This study provides the first evidence for a therapeutic potential of the vagus nerve and the "nicotinic anti-inflammatory pathway" in attenuating inflammation and injury during experimental pancreatitis.