Intestinal Serotonin Release, Sensory Neuron Activation, and Abdominal Pain in Irritable Bowel Syndrome
Intestinal Serotonin Release, Sensory Neuron Activation, and Abdominal Pain in Irritable Bowel Syndrome
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DOI：
10.1038/ajg.2011.86
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发表时间：
2011-07-01
影响因子：
9.8
通讯作者：
Barbara, Giovanni
中科院分区：
文献类型：
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作者：
Cremon, Cesare;Carini, Giovanni;Barbara, Giovanni
目的：5-羟色胺(5-羟色胺，5-羟色胺)代谢可能在肠道疾病中发生改变，包括肠易激综合征(IBS)。我们评估了IBS患者和健康对照组(HCS)结肠5-羟色胺阳性细胞的数量；粘膜5-羟色胺的释放量；它们与肥大细胞计数、介质释放以及IBS症状的相关性；以及黏膜5-羟色胺对体外电生理反应的影响。IBS症状严重程度和频度均为0~4级。用免疫组织化学方法定量检测结肠活检组织中5-羟色胺阳性的肠嗜铬细胞和类胰蛋白酶阳性的肥大细胞。黏膜5-羟色胺和肥大细胞介质分别用高效液相色谱法和免疫酶分析法检测。结果：肠易激综合征患者肠系膜上5-羟色胺阳性细胞数显著高于正常对照组(0.37+/-0.16%vs.0.56+/-0.26%；P=0.039)，腹泻型肠易激综合征组5-羟色胺阳性细胞数显著高于便秘型肠易激综合征组(P=0.035)。与肥大相比，肠易激综合征患者的5-羟色胺释放显著增加10倍(P<；0.001)，且与肥大细胞计数相关。胃黏膜5-羟色胺释放量与腹痛程度呈正相关(r(S)=0.582，P=0.047)。5-HT3受体拮抗剂格拉司琼(P<；0.005)可显著抑制IBS大鼠空肠感觉传入放电的峰值，而不是曲线下面积(P<；0.005)。结论：IBS患者无论排便习惯如何，5-羟色胺自发释放均显著增加，且与肥大细胞计数和腹痛程度相关。我们的结果提示，5-羟色胺释放增加可能通过粘膜免疫激活参与了IBS腹痛的发生。
OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) metabolism may be altered in gut disorders, including in the irritable bowel syndrome (IBS). We assessed in patients with IBS vs. healthy controls (HCs) the number of colonic 5-HT-positive cells; the amount of mucosal 5-HT release; their correlation with mast cell counts and mediator release, as well as IBS symptoms; and the effects of mucosal 5-HT on electrophysiological responses in vitro.METHODS: We enrolled 25 Rome II IBS patients and 12 HCs. IBS symptom severity and frequency were graded 0-4. 5-HT-positive enterochromaffin cells and tryptase-positive mast cells were assessed with quantitative immunohistochemistry on colonic biopsies. Mucosal 5-HT and mast cell mediators were assessed by high-performance liquid chromatography or immunoenzymatic assay, respectively. The impact of mucosal 5-HT on electrophysiological activity of rat mesenteric afferent nerves was evaluated in vitro.RESULTS: Compared with HCs, patients with IBS showed a significant increase in 5-HT-positive cell counts (0.37 +/- 0.16 % vs. 0.56 +/- 0.26 %; P = 0.039), which was significantly greater in patients with diarrhea-predominant IBS vs. constipation-predominant IBS (P = 0.035). Compared with HCs, 5-HT release in patients with IBS was 10-fold significantly increased (P < 0.001), irrespective of bowel habit, and was correlated with mast cell counts. A significant correlation was found between the mucosal 5-HT release and the severity of abdominal pain (r(s) = 0.582, P = 0.047). The area under the curve, but not peak sensory afferent discharge evoked by IBS samples in rat jejunum, was significantly inhibited by the 5-HT 3 receptor antagonist granisetron (P < 0.005).CONCLUSIONS: In patients with IBS, 5-HT spontaneous release was significantly increased irrespective of bowel habit and correlated with mast cell counts and the severity of abdominal pain. Our results suggest that increased 5-HT release contributes to development of abdominal pain in IBS, probably through mucosal immune activation.