Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
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DOI：
10.1136/gut.2006.113688
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发表时间：
2007-09-01
期刊：
影响因子：
24.5
通讯作者：
Sifrim, Daniel
中科院分区：
文献类型：
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作者：
Farre, Ricard;De Vos, Rita;Sifrim, Daniel
背景资料：在非糜烂性胃食管反流病患者中，当酸通过卵巢粘膜扩张的细胞间隙到达感觉神经末梢时，可发生胃灼热。紧张的生活事件可能会增加烧心感。在大鼠中，急性应激增加胃和肠粘膜的渗透性。我们研究了急性应激是否也能增加食管粘膜的通透性，并有助于扩张粘膜细胞间spaces.Methods：雄性Sprague -道利大鼠提交部分约束应力。将应激和对照大鼠的食管粘膜置于扩散室中。在用Krebs（对照）或HCl pH 2.0+胃蛋白酶1 mg/ml孵育组织后，评估对Cr-51-EDTA（400 Da）、异硫氰酸荧光素（FITC）-葡聚糖4000 Da（FD 4）和FITC-葡聚糖20 000 Da（FD 20）的渗透性。细胞间隙的直径进行了评估，使用透射电子显微镜。结果：急性应激增加粪便排出量，小肠通透性和血吸虫。对照组大鼠食管粘膜暴露于酸性胃蛋白酶并没有增加任何测试分子的渗透性。应激增加了粘膜下肥大细胞的数量，并增加了对最小分子的渗透性（22.8 +/- 7.1 pmol/cm（2）vs 5.8 +/- 2.1 pmol/cm（2））（p < 0.001）。应激大鼠的粘膜暴露于酸性胃蛋白酶显著增加了所有测试分子的渗透性。电子显微镜显示扩张的细胞间隙只在应激大鼠的粘膜（有和没有暴露于酸性胃蛋白酶）。结论：急性应激本身可以增加，食管粘膜通透性。食管粘膜的应激和暴露于酸性胃蛋白酶之间存在增强作用，导致通透性增加和细胞间隙扩张。
Background: In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces.Methods: Male Sprague - Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to Cr-51-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy.Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8 +/- 7.1 pmol/cm(2) vs 5.8 +/- 2.1 pmol/cm(2)) (p < 0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin).Conclusions: Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.