γ干扰素对缺氧肠上皮屏障功能影响及其机制

Effect of interferon-gamma on intestinal barrier function of epithelial cells under hypoxia

目的观察1干扰素（IFN-γ）对缺氧肠上皮细胞屏障功能的影响，探讨其分子机制。方法对HT-29细胞进行缺氧及IFN-γ处理，检测跨上皮电阻（TER）、缺氧诱导因子-1a（HIF-1a）蛋白及肠三叶因子（ITF）、黏蛋白3（mucin-3）、CD73、CD55、血小板活化因子受体（PAFR）mRNA表达的变化。结果缺氧＋IFN-γ使TER明显下降（较常氧和缺氧下降33．8％、28．3％），使HIF—1a蛋白较缺氧降低72．1％，使ITF、mucin-3、CD73、CD55、PAFRmRNA分别较缺氧降低53．3％、31．1％、74．6％、62．4％，但PAFRmRNA水平两组间差异无统计学意义（P〉0．05）。结论IFN-γ能使缺氧肠屏障功能降低，与IFN-γ使HIF-1a蛋白降低，并抑制HIF-1a下游的肠屏障调节因子密切相关。

Objective To investigate the effect of interferon-gamma （IFN-γ） on intestinal barrier function of epithelial cells under hypoxia. Methods Intestinal epithelial cells were randomly divided into normoxia group, hypoxia group and hypoxia plus IFN-γ group. Transepithelial electrical resistance （TER） was determined. Hypoxia inducible factor （HIF）-1γ protein expression and HIF-lct-induced intestinal bar- rier function regulators （ITF, mucin-3, CD73, CD55, PAFR） mRNA expression were assayed. Results TER in hypoxia plus IFN-γ, group was significantly decreased as compared with that in normoxia group （33.8%） and hypoxia group （28.3%）. HIF-1a protein expression in hypoxia plus IFN-γ group was decreased significantly by 72. 1%. The mRNA expression of ITF, mucin-3, CD73 and CD55 in hypoxia plus IFN-γ group was decreased significantly by 53.3% , 31.1% , 74. 6% and 62.4% respectively as compared with that in hypoxia group, but there was no obvious difference in the PAFR mRNA expression between hypoxia group and hypoxia plus IFN-γ group （P 〉 0. 05 ）. Conclusion IFN-γ can aggravate intestinal barrier dysfunction by down-regulating the HIF-1a protein expression and HIF-1a-induced intestinal barrier function tegulators.