RESUMEN
Neonates with intrauterine growth restriction (IUGR) show lower efficiency of nutrient utilization compared to normal birth weight (NBW) newborns. This study was conducted using neonatal piglets as a model to test the hypothesis that IUGR affects the intestinal barrier function, intestinal structure, and antioxidant system development during the suckling period. The small intestinal mucosae were obtained from IUGR and NBW littermates in the suckling period (d 0, 3, 8, and 19 postnatal). The epithelial barrier function was assessed by FITC-dextran 4 (FD4) and horseradish peroxidase (HRP) fluxes across the epithelium, histomorphologic measurements, and expression of tight-junction proteins. Redox status represented by the glutathione disulfide/glutathione ratio and malondialdehyde concentrations was determined, whereas mRNA expressions of some redox-sensitive proteins were quantified. Results showed that IUGR piglets exhibited a 2-fold higher intestinal permeability in the proximal small intestine on d 0 (P < 0.05), and this difference between IUGR and NBW piglets was widened to 3 and 4 times for FD4 and HRP, respectively (P < 0.05), on d 3. In accordance, expression of occludin was down-regulated at the transcriptional level in IUGR piglets at d 0 and 19 (P < 0.01). Furthermore, the transcription of heme oxygenase 1, catalase, and thioredoxin reductase genes was down-regulated in IUGR piglets, mainly on postnatal d 0 and 19 (P < 0.01). It appears that IUGR subjects have a lower capacity to mount an antioxidant response in the early postnatal period. Collectively, these results add to our understanding of the mechanisms responsible for intestinal dysfunction in IUGR neonates.
Asunto(s)
Retardo del Crecimiento Fetal/metabolismo , Regulación de la Expresión Génica , Mucosa Intestinal/metabolismo , ARN Mensajero/biosíntesis , Animales , Antioxidantes/metabolismo , Femenino , Retardo del Crecimiento Fetal/patología , Hemo-Oxigenasa 1/biosíntesis , Mucosa Intestinal/patología , Oxidación-Reducción , Permeabilidad , Embarazo , Porcinos , Reductasa de Tiorredoxina-Disulfuro/biosíntesisRESUMEN
Scratch (scrt) genes are neural-specific in mammals, but their homologues have not been well studied in non-mammalian vertebrates. In this report, we isolated three zebrafish scrt genes, scratch1a (scrt1a), scratch1b (scrt1b), and scratch2 (scrt2), which belong to the Snail superfamily of zinc finger transcription factors. Spatiotemporal expression analysis revealed that scrt1a and scrt2 were initially detected in the central nervous system (CNS) during early somitogenesis while scrt1b was first detectable in neuronal clusters in the brain during late somitogenesis. Interestingly, scrt-expressing cells largely overlapped with huC-positive differentiating neurons and partially with neurogenin1-positive neuronal precursor cells. In addition, scrt-expressing cells were dramatically increased in mind bomb, a neurogenic mutant. Taken together, these results suggest that each zebrafish scrt gene is specifically expressed in neuronal cells and may be involved in differentiation of distinct neuronal populations in the vertebrate nervous system.