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.

Objective To discover the mechanism of Sirtuin1 (SIRT1)-mediated NF-κB pathway in the protection of necrotizing enterocolitis (NEC) in neonatal mice. 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 mice was recorded. Hematoxylin & eosin (HE) staining was performed to observe the pathological changes of intestines. Furthermore, western blotting, Enzyme-linked immuno sorbent assay (ELISA), and real-time quantitative polymerase chain reaction (qRT-PCR) were conducted to measure the protein and gene expression, while corresponding kits 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 score of NEC was higher in the NEC + EX527 group but was lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was down-regulated, with an increase in p65 nuclear translocation. Also, MDA increased and GPx decreased in the intestines of NEC mice, with the up-regulations of IL-6, IL-1β and TNF-α, as well as the down-regulations of ZO-1, occludin and claudin-4 in the intestines. However, changes above could be improved by PDTC, which would be further reversed by EX527. Conclusion SIRT1 could mitigate inflammation and oxidative stress response and improve the intestinal permeability by mediating NF-κB pathway, playing an important role in the alleviation of NEC.

Aims Hypoxic-ischaemic brain damage (HIBD) remains a common sequelae of various nervous system diseases. Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) transplantation was considered to be promising in treating HIBD. However, it remains open the best administration way to transplant hUC-MSCs. In this study, we systematically compared the three administration ways —— the intravenous, the intracerebral and the intranasal administration for the first time to guide the best clinical practice. Methods The HIBD rat models were built on postnatal day 7(PN7). And rats were divided into five groups: sham, HIBD, HIBD + IV (intravenous administration), HIBD + IN (intranasal administration) and HIBD + IC (intracerebral administration). The behavioral experiments were used to compare the motor function、learning and memory function improvement of three administration ways, where the motor function of rats on PN10 and PN21 were evaluated by hanging wire and vertical pole test, and the learning and memory function of rats were evaluated by the Morris water maze (MWM) test. Moreover, the pathological tests were used to compare the pathological repair effects of three administration ways: the morphological changes of brain tissue were tested by Haematoxylin and eosin staining; the proliferation of reactive astrocytes were compared by detecting the expression of glial fibrillar acidic protein (GFAP), and the number of neuronal apoptosis in cortex and hippocampus were compared by TUNEL staining. Results The motor function of rats in HIBD group was significantly lower than that in sham group on the PN10, both in hanging wire and vertical pole tests (P < 0.0001). This shows the effectiveness of our HIBD model. According to the hanging wire test, the improvement of motor function in HIBD + IN group and HIBD + IC group were more obvious than that HIBD + IV group (P < 0.05), but no significant difference between HIBD + IN group and HIBD + IC group(P > 0.05).