Y Chen1,2, Y Koike1, H Miyake1, B Li1, C Lee1, A Hock1, A Zani3, A Pierro4. 1. Division of General and Thoracic Surgery, Programme of Physiology and Experimental Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada. 2. Department of Pediatric Surgery, KK Women's and Children's Hospital, Singapore, Singapore. 3. Division of General and Thoracic Surgery, Programme of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada. 4. Division of General and Thoracic Surgery, Programme of Physiology and Experimental Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada. agostino.pierro@sickkids.ca.
Abstract
PURPOSE: Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. METHODS: Neonatal mice were studied in three groups. Control (N = 9): breast feeding; NEC A (N = 8), gavage feeding + lipopolysaccharide (LPS) + preprandial hypoxia; and NEC B (N = 9), feeding + LPS + postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. RESULTS: NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p < 0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p < 0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p < 0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. CONCLUSION: Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.
PURPOSE: Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. METHODS: Neonatal mice were studied in three groups. Control (N = 9): breast feeding; NEC A (N = 8), gavage feeding + lipopolysaccharide (LPS) + preprandial hypoxia; and NEC B (N = 9), feeding + LPS + postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. RESULTS: NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p < 0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p < 0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p < 0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. CONCLUSION: Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.
Authors: Niloofar Ganji; Bo Li; Irfan Ahmad; Alan Daneman; Poorva Deshpande; Vijay Dhar; Simon Eaton; Ricardo Faingold; Estelle B Gauda; Nigel Hall; Salhab El Helou; Mustafa H Kabeer; Jae H Kim; Alice King; Michael H Livingston; Eugene Ng; Martin Offringa; Elena Palleri; Mark Walton; David E Wesson; Tomas Wester; Rene M H Wijnen; Andrew Willan; Rosanna Yankanah; Carlos Zozaya; Prakesh S Shah; Agostino Pierro Journal: Pediatr Surg Int Date: 2022-03-16 Impact factor: 1.827
Authors: Bo Li; Carol Lee; Tali Filler; Alison Hock; Richard You Wu; Qi Li; Shigang Chen; Yuhki Koike; Wan Ip; Lijun Chi; Elke Zani-Ruttenstock; Pekka Määttänen; Tanja Gonska; Paul Delgado-Olguin; Augusto Zani; Philip M Sherman; Agostino Pierro Journal: Sci Rep Date: 2017-05-11 Impact factor: 4.379