Abstract
Necrotizing enterocolitis (NEC) is a lethal gastrointestinal tract disease that occurs in premature infants. Adenosine receptor A2B (A2BR) regulates the inflammation cytokine secretion and immune cell infiltration in the colonic pathophysiology conditions. In the present study, we aim to determine the roles of A2BR in the development of NEC. A NEC rat model was established and treated with A2BR agonist-BAY60-6583 or A2BR antagonist-PSB1115. Animals in the control group were free from any interventions. Our results showed that the inhibition of A2BR PSB1115 improved intestinal injury and inflammation in newborn NEC rats. The expression levels of caspase-3 and the ratio of apoptotic cells were upregulated in NEC rats, and these indices were downregulated after treating with PSB1115 but further upregulated by BAY60-6583. Meanwhile, a similar trend was also witnessed in the changes of MPO activities and proinflammatory cytokines including IL-6, IFN-γ, and TNF-α. However, the anti-inflammatory cytokine IL-10 in the NECP group was significantly higher than that in the NEC and NECB groups (p < 0.05, respectively). Moreover, the expression of Ki67 was significantly increased in the NECP group as compared with those of the NEC and the NECB groups (p < 0.05, respectively). Collectively, our study suggested that the inhibition of A2BR attenuates NEC in the neonatal rat, at least partially through the modulation of inflammation and the induction of epithelial cell proliferation.
Highlights
Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal emergency in the neonates
We aim to investigate the role of A2BR in the NEC using its selective agonist and antagonist in rats
We measured the expression levels of A2BR during NEC by IHC, and we found that A2BR expression was upregulated in the NEC group, which was more significant in the NECB group when compared to the control
Summary
Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal emergency in the neonates. It usually occurs between 27 and 34 weeks after conception, especially in the preterm infants with a very low birth weight < 1000 g [1, 2]. With the updated modern care and therapy methods, overall survival has not changed and the average mortality from NEC is 2030% [4]. It was recognized that the increased production of inflammatory mediators, activated receptors which are termed inflammatory cascades, is responsible for the development of NEC[7, 8]. Epithelial injury and intestinal barrier damage were the typical pathological change in NEC, but the underlying mechanism has not been fully understood [9, 10].
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