Abstract
Background: Necrotizing enterocolitis [NEC] is a deadly disease in preterm human neonates. Since 1975, the newborn rat has been the preferred animal model of human NEC. Why the newborn rat model develops manifestations like human NEC remains elusive.
Objective: We hypothesized that the newborn rat has a deficiency in the expression of endogenous peptide antibiotics in the ileum, the major site of NEC, and thus renders the ileum susceptible to intra-luminal bacterial overgrowth.
Design/Methods: Stomach, jejunum, ileum, and colon were recovered from 3-day-old, 7-day-old, and adult rats. Bowel specimens were pooled from 4 or more newborn rats. At least 3 separate litters of rats were studied. RNA was isolated from bowel and copy counts of cryptdin-5 and -7 [alpha-defensins], lysozyme, and secretory phospholipase A2 per microgram of RNA were quantified using the Roche Light Cycler.
Results: Cryptdins were found mostly in the small bowel. In 3-day-old rats, cryptdin-5 was not detected compared to the ileum of adult rats (P<.001), while cryptdin-7 was 25% of adult expression (P<.01). By 7 days of age, cryptdin-5 and -7 were 50 to 60% of the expression in adult ileum. Lysozyme and phospholipase A2 expression in ileum was similar in 3- and 7-day-old rats, and their expression was ∼70% and ∼45%, respectively, of the ileal RNA content for these antimicrobial peptides in adult rats.
Conclusions: Since cryptdins account for 70% of the antimicrobial activity against Escherichia coli in the ileum of adult mice, the low expression of cryptdins in 3-day-old rats correlates with the pathogenesis of NEC in this species. Moreover, this finding agrees with low expression of alpha-defensins in the human fetus at 24 weeks of gestation. We speculate these observations have meaning for the development of NEC in extremely preterm human infants.
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Sherman, M., Bennett, S., Chu, H. et al. 342 The Newborn Rat Model of Necrotizing Enterocolitis and Expression of Endogenous Peptide Antibiotics in Small Bowel. Pediatr Res 58, 413 (2005). https://doi.org/10.1203/00006450-200508000-00371
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DOI: https://doi.org/10.1203/00006450-200508000-00371