Hou Lian, Du Junbao, Li Jinxin, Luo Qing, Kang Quan
Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing, China.
PLoS One. 2025 Jun 26;20(6):e0324068. doi: 10.1371/journal.pone.0324068. eCollection 2025.
Necrotizing enterocolitis(NEC) is a prevalent and destructive illness in neonates. Nicotinamide N-methyltransferase (NNMT) and its derivative, 1-methylnicotinamide (1-MNA), are known to be significant in conditions such as cardiovascular inflammation and renal tubular damage, and 1-MNA has been recognized for its anti-inflammatory effects in various diseases. However, the involvement of NNMT and 1-MNA in the development of NEC remains unclear.
We collected intestinal tissues and blood samples from children with NEC and control subjects for biochemical analysis. The NEC rats were induced by hypoxic cold stimulation and lipopolysaccharide, and control, NEC and NEC + 1-MNA groups were established. Neonatal rats were executed on the fourth day and blood, intestinal and fecal specimens were taken for subsequent testing.
Elevated NNMT and 1-MNA were found in NEC children and NEC rats. Exogenous supplementation of 1-MNA to NEC rats reduced mortality, pathological and inflammatory damage, and inhibited activation of the TLR4-NF-κB pathway in neonatal rats. In addition, 1-MNA improved intestinal barrier function and modulated intestinal flora in NEC rats.
1-MNA attenuated NEC injury by seemingly inhibiting the TLR4-NF-κB pathway, improving intestinal barrier function and modulating intestinal flora. These findings suggest a potential therapeutic role for 1-MNA in NEC management.
坏死性小肠结肠炎（NEC）是新生儿中一种常见且具有破坏性的疾病。已知烟酰胺N-甲基转移酶（NNMT）及其衍生物1-甲基烟酰胺（1-MNA）在心血管炎症和肾小管损伤等病症中具有重要意义，并且1-MNA在多种疾病中的抗炎作用已得到认可。然而，NNMT和1-MNA在NEC发病过程中的作用仍不清楚。
我们收集了NEC患儿和对照受试者的肠道组织及血液样本进行生化分析。通过缺氧寒冷刺激和脂多糖诱导建立NEC大鼠模型，并设立对照组、NEC组和NEC + 1-MNA组。在出生后第四天处死新生大鼠，采集血液、肠道和粪便样本用于后续检测。
在NEC患儿和NEC大鼠中发现NNMT和1-MNA升高。对NEC大鼠外源性补充1-MNA可降低死亡率、减轻病理和炎症损伤，并抑制新生大鼠TLR4-NF-κB通路的激活。此外，1-MNA改善了NEC大鼠的肠道屏障功能并调节了肠道菌群。
1-MNA似乎通过抑制TLR4-NF-κB通路、改善肠道屏障功能和调节肠道菌群来减轻NEC损伤。这些发现提示1-MNA在NEC治疗中具有潜在的治疗作用。
