Qin Xiaofa, Caputo Francis J, Xu Da-Zhong, Deitch Edwin A
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
Shock. 2008 Mar;29(3):372-6. doi: 10.1097/shk.0b013e3181453f4e.
Loss of the gut barrier has been implicated in the pathogenesis of the multiple organ dysfunction syndrome, and, thus, understanding the intestinal barrier is of potential clinical importance. An important, but relatively neglected, component of the gut barrier is the unstirred mucus layer, which through its hydrophobic and other properties serves as an important barrier to bacterial and other factors within the gut lumen. Thus, the goal of this study was to establish a reproducible method of measuring mucosal hydrophobicity and test the hypothesis that conditions that decrease mucosal hydrophobicity are associated with increased gut permeability. Hydrophobicity was measured in various segments of normal gut by measuring the contact angle of an aqueous droplet placed on the mucosal surface using a commercial goniometer. Second, the effect of the mucolytic agent N-acetyl cysteine on mucosal hydrophobicity and gut permeability was measured, as was the effects of increasing periods of in vivo gut ischemia on these parameters. Gut ischemia was induced by superior mesenteric artery occlusion, and gut permeability was measured by the mucosal-to-serosal passage of fluoresceine isothiocyanate-dextran (4.3 kDa) (FD4) across the everted sacs of ileum. Intestinal mucosal hydrophobicity showed a gradual increase from the duodenum to the end of the ileum and remained at high level in the cecum, colon, and rectum. Both N-acetyl cysteine treatment and ischemia caused a dose-dependent decrease in mucosal hydrophobicity, which significantly correlated increased gut permeability. Mucosal hydrophobicity of the intestine can be reproducibly measured, and decreases in mucosal hydrophobicity closely correlate with increased gut permeability. These results suggest that mucosal hydrophobicity can be a reliable method of measuring the barrier function of the unstirred mucus layer and a useful parameter in evaluating the pathogenesis of gut barrier dysfunction.
肠道屏障的丧失与多器官功能障碍综合征的发病机制有关,因此,了解肠道屏障具有潜在的临床重要性。肠道屏障的一个重要但相对被忽视的组成部分是静止黏液层,它通过其疏水性和其他特性,作为肠道腔内细菌和其他因素的重要屏障。因此,本研究的目的是建立一种可重复的测量黏膜疏水性的方法,并检验黏膜疏水性降低的情况与肠道通透性增加相关的假设。通过使用商用测角仪测量放置在黏膜表面的水滴的接触角,来测量正常肠道各段的疏水性。其次,测量黏液溶解剂N-乙酰半胱氨酸对黏膜疏水性和肠道通透性的影响,以及体内肠道缺血时间延长对这些参数的影响。通过肠系膜上动脉闭塞诱导肠道缺血,通过异硫氰酸荧光素-葡聚糖(4.3 kDa)(FD4)在回肠外翻囊中从黏膜到浆膜的转运来测量肠道通透性。肠道黏膜疏水性从十二指肠到回肠末端逐渐增加,在盲肠、结肠和直肠中保持在高水平。N-乙酰半胱氨酸处理和缺血均导致黏膜疏水性呈剂量依赖性降低,这与肠道通透性增加显著相关。肠道黏膜疏水性可以被重复测量,黏膜疏水性的降低与肠道通透性增加密切相关。这些结果表明,黏膜疏水性可以作为一种可靠的测量静止黏液层屏障功能的方法,以及评估肠道屏障功能障碍发病机制的有用参数。