Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment
Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment
复制标题
DOI：
10.1152/ajpgi.00090.2006
复制
发表时间：
2006-11-01
影响因子：
4.5
通讯作者：
Dvorak, Bohuslav
中科院分区：
文献类型：
--
作者：
Clark, Jessica A.;Doelle, Sarah M.;Dvorak, Bohuslav
实验性坏死性小肠结肠炎时肠屏障衰竭：表皮生长因子治疗的保护作用。Am J Physiol胃肠病肝生理学291：G938-G949,2006。2006年6月22日首次出版；doi：10.1152/ajpgi.00090.2006。坏死性小肠结肠炎(NEC)是早产儿最常见的肠道疾病。虽然粘膜通透性增加和上皮结构改变与许多肠道疾病有关，但肠屏障功能在NEC发病机制中的作用目前尚不清楚。我们研究了NEC模型大鼠肠道屏障的结构和功能变化。此外，还观察了EGF对肠屏障功能的影响。将早产大鼠分为3组：配方饲料(DAME)组、配方饲料(NEC)组和配方饲料加500 ng/mlEGF组(NEC+EGF)，每组均暴露于窒息/3冷应激状态，形成NEC。检测NEC损伤部位末端回肠的通透性、杯状细胞密度、粘蛋白产生和紧密连接(TJ)蛋白的组成，并与未受NEC影响的近端空肠进行比较。与DF仔鼠相比，NEC组动物的肠道细胞旁通透性显著增加。NEC动物回肠杯状细胞形态、粘蛋白产生和TJ成分发生改变。EGF治疗显著降低肠细胞旁通透性，增加杯状细胞密度和粘蛋白的产生，并使两种主要的TJ蛋白-occludin和claudin-3在回肠中的正常表达。总而言之，实验性NEC与肠道屏障的破坏有关。EGF治疗通过促进杯状细胞的成熟和粘蛋白的产生以及TJ蛋白的正常表达来维持损伤部位的肠道完整性，从而改善肠道屏障功能。
Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol 291: G938-G949, 2006. First published June 22, 2006; doi:10.1152/ajpgi.00090.2006. - Necrotizing enterocolitis (NEC) is the most common intestinal disease of premature infants. Although increased mucosal permeability and altered epithelial structure have been associated with many intestinal disorders, the role of intestinal barrier function in NEC pathogenesis is currently unknown. We investigated the structural and functional changes of the intestinal barrier in a rat model of NEC. In addition, the effect of EGF treatment on intestinal barrier function was evaluated. Premature rats were divided into three groups: dam fed (DF), formula fed (NEC), or fed with formula supplemented with 500 ng/ml EGF (NEC + EGF); all groups were exposed to asphyxia/3cold stress to develop NEC. Intestinal permeability, goblet cell density, mucin production, and composition of tight junction (TJ) proteins were evaluated in the terminal ileum, the site of NEC injury, and compared with the proximal jejunum, which was unaffected by NEC. Animals with NEC had significantly increased intestinal paracellular permeability compared with DF pups. Ileal goblet cell morphology, mucin production, and TJ composition were altered in animals with NEC. EGF treatment significantly decreased intestinal paracellular permeability, increased goblet cell density and mucin production, and normalized expression of two major TJ proteins, occludin and claudin-3, in the ileum. In conclusion, experimental NEC is associated with disruption of the intestinal barrier. EGF treatment maintains intestinal integrity at the site of injury by accelerating goblet cell maturation and mucin production and normalizing expression of TJ proteins, leading to improved intestinal barrier function.