Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome
Activation of Human Enteric Neurons by Supernatants of Colonic Biopsy Specimens From Patients With Irritable Bowel Syndrome
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DOI：
10.1053/j.gastro.2009.07.005
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发表时间：
2009-10-01
期刊：
影响因子：
29.4
通讯作者：
Schemann, Michael
中科院分区：
文献类型：
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作者：
Buhner, Sabine;Li, Qin;Schemann, Michael
背景与目的：肠易激综合征(IBS)的病理特征包括粘膜细胞内容物和介质释放的改变，这可能改变附近粘膜下神经元的信号。方法：应用电压敏感染料成像技术，记录IBS患者粘膜活检组织中释放的介质对76例人结肠组织1207个粘膜下神经元胞体的影响。收集7例腹泻型IBS(D-IBS)、4例便秘型IBS(C-IBS)和4例健康对照的结肠粘膜活检组织培养上清液。测定培养上清液中5-羟色胺、组胺和类胰蛋白酶浓度及固有层肥大细胞密度。结果：与对照组相比，IBS上清液可显著增加58%的人粘膜下神经元的放电频率。对IBS上清液有反应的神经元的中位数尖峰频率为2.4赫兹，而对照上清液为0赫兹。C-IBS和D-IBS的培养上清液可诱发相似的棘波放电。组胺受体(H1-H3)拮抗剂、5-HT3受体拮抗剂和蛋白酶抑制剂均可抑制IBS上清液的激活作用。培养上清液中的5-羟色胺、组胺和类胰蛋白酶水平与上清液诱导的尖峰放电有关。IBS组的肥大细胞密度、培养上清液中组胺和类胰蛋白酶水平均高于对照组。结论：IBS患者粘膜活检组织中释放的介质可激活人粘膜下神经元。这种激活需要组胺、5-羟色胺和蛋白水解酶，但与IBS亚型无关。肠黏膜和肠神经系统之间信号的改变可能参与了IBS的发病机制。
BACKGROUND & AIMS: Pathological features in irritable bowel syndrome (IBS) include alterations in mucosal cell content and mediator release that might alter signaling to nearby submucosal neurons. METHODS: Voltage sensitive dye imaging was used to record the effects of mediators, released from mucosal biopsies of IBS patients, on cell bodies of 1207 submucosal neurons from 76 human colonic tissue specimens. Supernatants, containing these mediators, were collected following incubation with colonic mucosal biopsies from 7 patients with diarrhea-predominant IBS (D-IBS), 4 with constipation-predominant IBS (C-IBS), and 4 healthy controls. Serotonin, histamine and tryptase concentrations in supernatants and lamina propria mast cell density were determined. RESULTS: In contrast to controls, IBS supernatants significantly increased the rate of spike discharge in 58% of human submucosal neurons. Neurons that responded to IBS supernatant had a median spike frequency of 2.4 Hz compared to 0 Hz for control supernatants. Supernatants from C-IBS and D-IBS evoked similar spike discharge. The activation induced by IBS supernatants was inhibited by histamine receptor (H1-H3) antagonists, 5-HT3 receptor antagonist, and protease inhibition. Serotonin, histamine and tryptase levels in supernatants correlated with the spike discharge induced by the supernatants. Mast cells density as well as histamine and tryptase levels in supernatants were higher in IBS than in controls. CONCLUSIONS: Mediators released from mucosal biopsies of IBS patients can activate human submucosal neurons. The activation required histamine, serotonin and proteases but was not associated with IBS subtype. Altered signaling between mucosa and the enteric nervous system might be involved in IBS pathogenesis.