Vitamin A protects the preterm lamb diaphragm against adverse effects of mechanical ventilation
Methods: Preterm lambs delivered operatively at ∼131 days gestation (full gestation: 150 days) received respiratory support by synchronized intermittent mandatory ventilation for 3 days. Lambs in the treated group received daily (24 h) enteral doses of 2500 IU/kg/day vitamin A combined with 250 IU/kg/day retinoic acid (VARA) during MV, while MV control lambs received saline. Unventilated fetal reference lambs were euthanized at birth, without being allowed to breathe. The fetal diaphragm was collected to quantify mRNA levels of myosin heavy chain (MHC) isoforms, atrophy genes, antioxidant genes, and pro-inflammatory genes; to determine ubiquitin proteasome pathway activity; to measure the abundance of protein carbonyl, and to investigate metabolic signaling.
Results: Postnatal MV significantly decreased expression level of the neonatal MHC gene but increased expression level of MHC IIx mRNA level (p < 0.05). Proteasome activity increased after 3 days MV, accompanied by increased MuRF1 mRNA level and accumulated protein carbonyl abundance. VARA supplementation decreased proteasome activity and FOXO1 signaling, down-regulated MuRF1 expression, and reduced reactive oxidant production.
Conclusion: These findings suggest that 3 days of MV results in abnormal myofibrillar composition, activation of the proteolytic pathway, and oxidative injury of diaphragms in mechanically ventilated preterm lambs. Daily enteral VARA protects the preterm diaphragm from these adverse effects.
History
Publication title
Frontiers in PhysiologyVolume
9Article number
1119Number
1119Pagination
1-13ISSN
1664-042XDepartment/School
Menzies Institute for Medical ResearchPublisher
Frontiers Research FoundationPlace of publication
SwitzerlandRights statement
Copyright 2018 Song, Dahl, Leavitt, Alvord, Bradford, Albertine and Pillow. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open