Department of Pediatrics, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.
Food Funct. 2023 Apr 24;14(8):3769-3778. doi: 10.1039/d2fo02400d.
Necrotizing enterocolitis (NEC) is a life-threatening risk to the health of neonates, but thus far, there is no very effective treatment. Although many studies have confirmed the therapeutic role of peptides in diseases, the effect of peptides in NEC remains poorly understood. This study investigated the role of casein-derived peptide YFYPEL in NEC cells and animal models. We synthesized YFYPEL and analysed its protective effects on NEC both . YFYPEL integration in the intestine increased rat survival and clinical conditions, lowered the incidence of NEC, alleviated bowel inflammation, and enhanced intestinal cell migration. Furthermore, YFYPEL significantly decreased interleukin 6 expression and increased intestinal epithelial cell migration. Moreover, YFYPEL alleviated intestinal epithelial cell dysfunction through the PI3K/AKT pathway, as demonstrated by western blotting and bioinformatics analysis. A selective PI3K activator reversed the protective effect of YFYPEL on lipopolysaccharide-stimulated intestinal epithelial cells. Our study showed that YFYPEL reduced inflammatory cytokine expression and enhanced migration by regulating the PI3K/AKT pathway. The use of YFYPEL may thus develop into a novel modality in NEC treatment.
坏死性小肠结肠炎 (NEC) 是新生儿健康面临的严重威胁，但迄今为止，尚无非常有效的治疗方法。尽管许多研究已经证实了肽类在疾病中的治疗作用，但肽类在 NEC 中的作用仍知之甚少。本研究探讨了酪蛋白衍生肽 YFYPEL 在 NEC 细胞和动物模型中的作用。我们合成了 YFYPEL 并分析了它对 NEC 的保护作用。YFYPEL 在肠道中的整合增加了大鼠的存活率和临床状况，降低了 NEC 的发生率，减轻了肠道炎症，并增强了肠道细胞迁移。此外，YFYPEL 显著降低了白细胞介素 6 的表达并促进了肠上皮细胞的迁移。此外，通过 Western blot 和生物信息学分析，YFYPEL 通过 PI3K/AKT 通路减轻了肠道上皮细胞的功能障碍。选择性 PI3K 激活剂逆转了 YFYPEL 对脂多糖刺激的肠上皮细胞的保护作用。我们的研究表明，YFYPEL 通过调节 PI3K/AKT 通路减少炎症细胞因子的表达并增强迁移。因此，使用 YFYPEL 可能成为治疗 NEC 的一种新方法。
