Large intestine permeability is increased in patients with compensated liver cirrhosis
Large intestine permeability is increased in patients with compensated liver cirrhosis
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DOI：
10.1152/ajpgi.00330.2013
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发表时间：
2014-01-01
影响因子：
4.5
通讯作者：
Jonkers, Daisy M. A. E.
中科院分区：
文献类型：
--
作者：
Pijls, Kirsten E.;Koek, Ger H.;Jonkers, Daisy M. A. E.
肠屏障功能障碍，促进细菌和细菌产物的移位，在肝硬化及其并发症的病理生理学中起重要作用。在肝硬化患者中已经发现肠通透性增加，但是关于代偿性肝硬化患者的小肠和大肠通透性和紧密连接（TJ）的数据很少。我们的目的是研究与健康对照组相比，稳定代偿期肝硬化患者的小肠和大肠通透性，并在十二指肠和乙状结肠水平评估粘膜活检组织中TJ蛋白的表达。采用多糖试验评估了26例代偿期肝硬化患者和27例匹配对照组的肠道通透性。十二指肠和乙状结肠活检可从一个亚组获得，用于分别通过qRT-PCR和ELISA分析关键TJ蛋白的基因转录和表达。代偿性肝硬化患者和对照组之间的0-5小时尿蔗糖排泄中位数和乳果糖/鼠李糖比率相当，而这些患者的5-24小时尿三氯蔗糖/赤藓糖醇比率增加。在十二指肠活检组织中发现了claudin-3的基因转录下调，在乙状结肠活检组织中发现了claudin-4的基因转录下调，并且在蛋白水平上，在十二指肠和乙状结肠活检组织中occludin的表达显著增加。这项研究表明，胃十二指肠和小肠的渗透性没有改变，而大肠的渗透性增加，在稳定的代偿性肝硬化患者。只有有限的改变被发现关于TJ蛋白在小肠和大肠的表达。
Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine.