Abstract
Objective To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB)
pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice.
Materials and Methods Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine
dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded.
Hematoxylin and eosin (HE) staining was performed to observe the pathological changes
in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay,
and real-time quantitative polymerase chain reaction were conducted to measure the
protein and gene expression, while corresponding kits were used to detect the levels
of oxidative stress indicators.
Results PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC
group, the histological NEC score was higher in the NEC + EX527 group but lower in
the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated,
with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased
and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation
of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as the downregulation
of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could
be improved by PDTC, which could be further reversed by EX527.
Conclusion SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal
permeability by mediating the NF-κB pathway, playing an important role in the alleviation
of NEC.
Keywords
neonatal NEC - SIRT1 - NF-κB - inflammation - oxidative stress
