Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis
Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis
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DOI：
10.1016/s0016-5085(99)70126-5
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发表时间：
1999-02-01
期刊：
影响因子：
29.4
通讯作者：
Schulzke, JD
中科院分区：
文献类型：
--
作者：
Schmitz, H;Barmeyer, C;Schulzke, JD
背景与目的：溃疡性结肠炎（UC）中腹泻的机制仍不清楚。对溃疡性结肠炎（UC）的上皮屏障功能及转运特性进行了功能和结构方面的表征。
方法：通过交流电阻抗分析对溃疡性结肠炎患者发炎的乙状结肠上皮进行研究，以确定纯上皮电阻，作为肠道屏障功能的一项指标。通过冷冻断裂电子显微镜对紧密连接（TJ）结构进行研究。
结果：尽管在溃疡性结肠炎中肠壁总电阻降低了50%，但阻抗分析揭示出更为显著的屏障缺陷。上皮电阻从95±5Ω·cm²降至20±3Ω·cm²，而在常规分析中，这一变化被炎症导致的上皮下电阻从14±1Ω·cm²增加到36±3Ω·cm²所掩盖。与此同时，溃疡性结肠炎中上皮细胞紧密连接结构发生了改变。表面的条索数量从6.94±0.25减少到4.76±0.47，隐窝处从7.26±0.31减少到5.46±0.37。
结论：溃疡性结肠炎中发炎的结肠黏膜屏障功能受损，其程度比之前所认为的要严重得多。紧密连接结构的改变导致了这种屏障缺陷，由于反向渗漏增加，可减少净离子转运。因此，渗漏 - 通量机制是溃疡性结肠炎中腹泻的原因之一。
Background & Aims: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. Methods: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. Results: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 Omega . cm(2), which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 Omega . cm(2) caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. Conclusions: The inflamed colonic mucosa in UC has an impaired barrier function that is much move pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.