Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons
Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons
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DOI：
10.1111/nmo.12000
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发表时间：
2012-12-01
影响因子：
3.5
通讯作者：
Barbara, G.
中科院分区：
文献类型：
--
作者：
Balestra, B.;Vicini, R.;Barbara, G.
背景 粘膜环境中释放的介质被认为与肠易激综合征 (IBS) 患者的内脏过敏和腹痛有关。然而，它们对肌间神经元的影响仍然悬而未决。方法 从 IBS 患者和对照患者的降结肠中获取粘膜活检组织。通过免疫组织化学方法鉴定粘膜肥大细胞。通过选择性受体拮抗剂和抑制剂，在体外评估了自发释放的粘膜介质对豚鼠电刺激纵向肌肌间神经丛（LMMP）制剂的影响。主要结果 与对照组相比，IBS 患者的肥大细胞计数有所增加。将IBS粘膜介质应用于LMMP可增强胆碱能抽搐收缩，这种效应与肥大细胞计数直接相关。前列腺素 D2 拮抗剂 BW A868C 增强的收缩被抑制 50.3%，TRPV1 拮抗剂辣椒西平和 HC-030031 分别抑制 31.3% 和 39%，嘌呤能 P2X 拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸分别抑制 60.5%。相反，血清素1-4、组胺1-3、速激肽1-3受体阻断和丝氨酸蛋白酶抑制则没有显着效果。结论与推论 IBS 患者的结肠粘膜介质会兴奋肌间胆碱能运动神经元。这些效应与肥大细胞计数相关，并由前列腺素受体、TRPV1 和 P2X 受体的激活介导。这些结果支持粘膜炎症介质和肥大细胞激活在 IBS 运动功能改变中的作用。
Background Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled. Methods Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors. Key Results Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect. Conclusions & Inferences Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS.