Intestinal barrier dysfunction in human necrotizing enterocolitis.
Intestinal barrier dysfunction in human necrotizing enterocolitis.
复制标题
人坏死性小肠结肠炎中的肠屏障功能障碍。
DOI：
10.1016/j.jpedsurg.2016.09.011
复制
发表时间：
2016-12
影响因子：
2.4
通讯作者：
Ma TY
中科院分区：
文献类型：
--
作者：
Moore SA;Nighot P;Reyes C;Rawat M;McKee J;Lemon D;Hanson J;Ma TY
肠屏障功能障碍与坏死性小肠结肠炎（NEC）有关，但尚未在人类NEC中直接测量。在手术期间取出的小肠立即安装在Ussing室中。RT-PCR检测紧密连接（TJ）蛋白的mRNA表达。15名婴儿被纳入，5名患有NEC，10名患有其他诊断。平均跨上皮电阻（TER）在NEC标本中为11.61 ± 1.65 Ω/cm 2，切除边缘为23.36 ± 1.48 Ω/cm 2，对照组为46.48 ± 5.65 Ω/cm 2。渗透性标记甘露醇的平均通量在NEC中为0.23 ± 0.06 μMol/cm 2/h，在切除边缘为0.04 ± 0.01 μMol/cm 2/h，在对照组织中为0.017 ± 0.004 μMol/cm 2/h（p < 0.05）。RT-PCR分析显示在NEC感染的组织中TJ蛋白闭合蛋白的mRNA表达显著降低（p < 0.03相对于对照）。此外，肌球蛋白轻链激酶（MLCK）的mRNA表达，一个重要的调节TJ渗透性，增加NEC标本。这些研究首次表明，NEC肠组织具有增加的肠通透性，即使在看起来非常健康的切除区域。NEC中肠道通透性的增加似乎部分与occludin的减少和MLCK表达的增加有关。2级
Intestinal barrier dysfunction has been implicated in necrotizing enterocolitis (NEC), but has not been directly measured in human NEC. Small intestines removed during surgery were immediately mounted in an Ussing chamber. mRNA expression of tight junction (TJ) proteins was measured with RT-PCR. Fifteen infants were included, 5 with NEC and 10 with other diagnoses. Average transepithelial resistance (TER) was 11.61 ± 1.65 Ω/cm2 in NEC specimens, 23.36 ± 1.48 Ω/cm2 at resection margin, and 46.48 ± 5.65 Ω/cm2 in controls. Average flux of permeability marker mannitol was 0.23 ± 0.06 μMol/cm2 per h in NEC, 0.04 ± 0.01 μMol/cm2 per h at resection margin, and 0.017 ± 0.004 μMol/cm2 per h in control tissue (p < 0.05). RT-PCR analysis showed marked decrease in mRNA expression of a TJ protein occludin in NEC affected tissue (p < 0.03 vs. control). Additionally, mRNA expression of myosin light chain kinase (MLCK), an important regulator of TJ permeability, was increased in NEC specimens. These studies show for the first time that NEC intestinal tissue have increased intestinal permeability, even at grossly healthy-appearing resection areas. The increase in intestinal permeability in NEC appeared to be related in part to a decrease in occludin and an increase in MLCK expression. Level 2.