Chou Hsiu-Chu, Chen Chung-Ming
Department of Anatomy and Cellular Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Exp Mol Pathol. 2017 Jun;102(3):415-421. doi: 10.1016/j.yexmp.2017.05.006. Epub 2017 May 12.
Animal studies have demonstrated that neonatal hyperoxia injures the distal small intestine and disrupts the intestinal barrier. This study evaluated the effects of brief hyperoxia exposure on intestinal function in newborn rats. Newborn Sprague-Dawley rat pups were exposed to room air or normobaric hyperoxia (85% O) for 1week. The rats were euthanized on Postnatal Day 7, and their terminal ilea and sera were collected for histological analyses and intestinal permeability measurements, respectively. Bacterial translocation to the liver and spleen under aerobic and anaerobic conditions was determined. The expression and localization of epithelial injury markers [intestinal fatty acid binding protein (I-FABP)], intestinal barrier proteins [occludin and zonula occludens (ZO)-1], and inflammation biomarkers [Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB)] were analyzed through immunofluorescence staining. The body weight at birth was comparable between the two groups. On Postnatal Day 7, the rats in the hyperoxic group exhibited significantly lower body weights, higher intestinal injury scores, lower numbers of goblet cells, higher I-FABP expression, lower occludin and ZO-1 expression, higher TLR4 and NF-κB expression, and higher intestinal permeability and bacterial translocation than did those in the room air group. The rats reared in O-enriched air displayed indistinct tight junction with widening of the paracellular spaces. Hyperoxia exposure injured the distal small intestine, disrupted the intestinal barrier, and impaired intestinal function in newborn rats. Hyperoxia-induced intestinal injury may be attributable to increased activity of the TLR4/NF-κB pathway during the postnatal period.
动物研究表明，新生儿高氧会损伤远端小肠并破坏肠道屏障。本研究评估了短暂暴露于高氧环境对新生大鼠肠道功能的影响。将新生的斯普拉格-道利大鼠幼崽暴露于室内空气或常压高氧（85%氧气）环境中1周。在出生后第7天对大鼠实施安乐死，并分别收集其回肠末端和血清用于组织学分析和肠道通透性测量。测定了需氧和厌氧条件下细菌向肝脏和脾脏的移位情况。通过免疫荧光染色分析了上皮损伤标志物[肠脂肪酸结合蛋白（I-FABP）]、肠道屏障蛋白[闭合蛋白和紧密连接蛋白（ZO）-1]以及炎症生物标志物[Toll样受体4（TLR4）和核因子-κB（NF-κB）]的表达和定位。两组出生时的体重相当。在出生后第7天，高氧组大鼠的体重显著低于室内空气组，肠道损伤评分更高，杯状细胞数量更少，I-FABP表达更高，闭合蛋白和ZO-1表达更低，TLR4和NF-κB表达更高，肠道通透性和细菌移位也更高。饲养在富氧空气中的大鼠紧密连接不清晰，细胞旁间隙增宽。暴露于高氧环境会损伤新生大鼠的远端小肠，破坏肠道屏障并损害肠道功能。高氧诱导的肠道损伤可能归因于出生后TLR4/NF-κB信号通路活性增加。
