| Description |
Premature neonates supported by invasive mechanical ventilation (IMV) are at increased risk of necrotizing enterocolitis (NEC). NEC is characterized by disruption to the immature intestinal barrier and enterocyte damage. We previously showed that preterm lambs managed by IMV for 21 days have feeding intolerance, poor weight gain and injury to the distal ileum that resembles NEC. In contrast, preterm lambs managed by non-invasive support (NIS) for 21 days tolerate feedings, have better postnatal growth and better gut histology. The distinct outcomes of preterm lambs managed by IMV and NIS provide an opportunity to evaluate the impact of variables associated with IMV, such as poor postnatal nutrition and sedation, on gut integrity. Using the positive outcome group NIS, preterm lambs received restricted enteral intake (NIS+RN), or sedation (NIS+ES) at levels matched to that of IMV-managed preterm lambs. The transcription factor PPARγ is required for gut integrity. Transcriptional targets of PPARγ, also important for gut barrier integrity, are FABP2 and the tight junction protein occludin. We hypothesize that in preterm lambs, IMV, NIS+RN and NIS+ES reduce gut integrity in association with decreased ileal expression of PPARγ, FABP2 and occludin. To test our hypothesis, we studied six groups of preterm lambs: IMV or NIS for 3 or 21 days, and NIS+RN and NIS+ES for 21 days. A reference group was unventilated term lambs. Expression of PPARγ, FABP2 and occludin was measured in ileal tissue. Preterm lambs managed by IMV and NIS+RN, had impaired postnatal growth and reduced expression of PPARγ and FABP2 compared to preterm lambs managed by NIS. Preterm lambs managed by NIS+ES did not have feeding intolerance or poor postnatal growth, but did have reduced PPARγ and FABP2 expression compared to preterm lambs managed by NIS. Contrary to our hypothesis, occludin protein abundance was not impacted by mode of ventilation, nutrition or sedation. In conclusion, IMV, NIS+RN and NIS-ES decreased PPARγ and FABP2 expression in the preterm lamb ileum. Disruption of PPARγ and FABP2 expression by IMV and inadequate nutrition may result in detrimental effects on gut integrity and contribute to the observed NEC-like phenotype in preterm lambs. |
