Prevention of Necrotizing Enterocolitis through Milk Polar Lipids Reducing Intestinal Epithelial Apoptosis

J Agric Food Chem. 2020 Jul 1;68(26):7014-7023. doi: 10.1021/acs.jafc.0c02629. Epub 2020 Jun 19.

Abstract

Neonatal necrotizing enterocolitis (NEC) is a common and devastating disease. The objective of this research was to investigate the protective mechanisms of milk polar lipids (MPLs) on the attenuation of lipopolysaccharides (LPS)-induced intestinal inflammation and apoptosis. MPLs were extracted from buttermilk and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A neonatal NEC rat model was used to investigate the effects of MPLs on NEC and its underlying mechanisms. Hematoxylin-eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay were used to observe intestinal morphological changes and intestinal epithelial cell apoptosis, which showed that MPLs could reduce NEC symptoms and intestinal apoptosis. The expressions of IL-6, IL-8, and TNF-α in the MPL group was significantly downregulated (P < 0.05), and the expression levels of IL-10 were significantly upregulated (P < 0.05). At the same time, MPLs also significantly reduced (P < 0.05) activation of the LPS-induced TLR4/NF-κB signaling pathway. Furthermore, MPLs inhibit apoptosis by reducing the expressions of Bax, caspase-9, and caspase-3 and by increasing the expression of Bcl-2. In conclusion, MPLs could reduce NEC symptoms in mice by inhibiting cell inflammation and protecting against intestinal apoptosis.

Keywords: NF-κB pathway; apoptosis; cytokines; milk polar lipids; neonatal necrotizing enterocolitis.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Buttermilk / analysis
  • Enterocolitis, Necrotizing / genetics
  • Enterocolitis, Necrotizing / immunology
  • Enterocolitis, Necrotizing / prevention & control*
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Female
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Lipids / administration & dosage*
  • Lipids / chemistry
  • Male
  • Mice
  • Milk / chemistry*
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Lipids
  • NF-kappa B
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha