Intestinal barrier dysfunction in human necrotizing enterocolitis

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• 作者：Sarah A. Moore^a ; ¹ ; Prashant Nighot^b ; ¹ ; Cynthia Reyes^a ; ^{CYReyes@salud.unm.edu} ; Manmeet Rawat^b ; Jason McKee^a ; David Lemon^a ; Joshua Hanson^c ; Thomas Y. Ma^b ; ^{TMa@salud.unm.edu}
• 关键词：Necrotizing enterocolitis ; Intestinal barrier function ; Tight junction ; Occludin
• 刊名：Journal of Pediatric Surgery
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：51
• 期：12
• 页码：1907-1913
• 全文大小：825 K
• 卷排序：51

文摘

Intestinal barrier dysfunction has been implicated in necrotizing enterocolitis (NEC), but has not been directly measured in human NEC.MethodsSmall intestines removed during surgery were immediately mounted in an Ussing chamber. mRNA expression of tight junction (TJ) proteins was measured with RT-PCR.ResultsFifteen 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.ConclusionThese 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 of evidenceLevel 2.