Sandle G I, Higgs N, Crowe P, Marsh M N, Venkatesan S, Peters T J
Epithelial Membrane Research Centre, University of Manchester, Salford, England.
Gastroenterology. 1990 Jul;99(1):97-105. doi: 10.1016/0016-5085(90)91235-x.
Electrolyte transport pathways in distal colonic mucosa from patients with noninflammatory and inflammatory (ulcerative colitis, Crohn's colitis) disease of the large bowel were studied in vitro with electrophysiological techniques. Noninflamed tissues exhibited substantial amiloride-sensitive electrogenic sodium transport. In contrast, inflamed but structurally intact tissues exhibited only a modest degree of electrogenic sodium transport, significant increases in total tissue conductance and apical membrane conductance, and a 100% increase in the arachidonic acid content of the cell membrane fraction of mucosal homogenates. Replacement of chloride with gluconate decreased total tissue conductance to a greater extent in inflamed than in noninflamed tissues, and total tissue conductance was higher in inflamed than in noninflamed tissues in the presence of transepithelial potassium and sodium gradients, suggesting enhanced mucosal "leakiness" to anions and cations in acute colitis. Apical addition of nystatin virtually abolished amiloride-sensitive apical sodium uptake in both groups, indicating that the ionophore formed channels in the apical membrane of noninflamed and diseased mucosa. Additional studies showed that mucosal inflammation decreased maximal activity of the basolateral sodium pump by 76%. Thus, defects in the biophysical properties of colonic epithelial cell membranes are likely to be important factors in the pathogenesis of diarrhea in ulcerative and Crohn's colitis.
采用电生理技术，对患有非炎症性和炎症性（溃疡性结肠炎、克罗恩结肠炎）大肠疾病患者的远端结肠黏膜中的电解质转运途径进行了体外研究。未发炎组织表现出大量对氨氯地平敏感的电生性钠转运。相比之下，发炎但结构完整的组织仅表现出适度的电生性钠转运、组织总电导和顶端膜电导显著增加，以及黏膜匀浆细胞膜部分的花生四烯酸含量增加100%。用葡萄糖酸盐替代氯化物在发炎组织中比在未发炎组织中更大程度地降低了组织总电导，并且在存在跨上皮钾和钠梯度的情况下，发炎组织中的组织总电导高于未发炎组织，这表明急性结肠炎中黏膜对阴离子和阳离子的“渗漏性”增强。在两组中，顶端添加制霉菌素几乎消除了对氨氯地平敏感的顶端钠摄取，表明离子载体在未发炎和患病黏膜的顶端膜中形成了通道。进一步的研究表明，黏膜炎症使基底外侧钠泵的最大活性降低了76%。因此，结肠上皮细胞膜生物物理特性的缺陷可能是溃疡性结肠炎和克罗恩结肠炎腹泻发病机制中的重要因素。
