肠道菌群失调被认为在坏死性小肠结肠炎(NEC)的发展中起作用。评估了JNK抑制肽(CPJIP)在治疗NEC中的功效。用CPJIP处理导致IEC-6细胞和NEC小鼠中p-JNK表达的显著降低。LPS刺激后,claudin-1、claudin-3、claudin-4和occludin的RNA和蛋白表达明显下降,随着这种下降被CPJIP管理部门逆转,除了claudin-3,在NEC小鼠中保持一致。此外,炎症因子TNF-α的表达水平,IL-1β和IL-6明显升高,在IEC-6细胞和NEC小鼠中添加CPJIP可有效缓解这种现象。CPJIP管理提高了生存率,改善显微肠粘膜损伤,并增加了NEC小鼠肠和结肠的总长度。此外,CPJIP处理导致FD-4、D-乳酸和DAO的血清浓度降低。此外,我们的结果表明,CPJIP可以有效抑制肠道细胞凋亡,促进肠道细胞增殖。这项研究代表了CPJIP增强紧密连接组件表达能力的第一个文件,抑制炎症反应,通过抑制JNK激活拯救肠道细胞命运,最终减轻肠道严重程度。这些发现表明,CPJIP有可能成为NEC治疗的有希望的候选人。
Intestinal dysbiosis is believed to play a role in the development of necrotizing enterocolitis (NEC). The efficacy of JNK-inhibitory peptide (CPJIP) in treating NEC was assessed. Treatment with CPJIP led to a notable reduction in p-JNK expression in IEC-6 cells and NEC mice. Following LPS stimulation, the expression of RNA and protein of claudin-1, claudin-3, claudin-4 and occludin was significantly decreased, with this decrease being reversed by CPJIP administration, except for claudin-3, which remained consistent in NEC mice. Moreover, the expression levels of the inflammatory factors TNF-α, IL-1β and IL-6 were markedly elevated, a phenomenon that was effectively mitigated by the addition of CPJIP in both IEC-6 cells and NEC mice. CPJIP administration resulted in improved survival rates, ameliorated microscopic intestinal mucosal injury, and increased the total length of the intestines and colon in NEC mice. Additionally, CPJIP treatment led to a reduction in serum concentrations of FD-4, D-lactate and DAO. Furthermore, our results revealed that CPJIP effectively inhibited intestinal cell apoptosis and promoted cell proliferation in the intestine. This study represents the first documentation of CPJIP\'s ability to enhance the expression of tight junction components, suppress inflammatory responses, and rescue intestinal cell fate by inhibiting JNK activation, ultimately mitigating intestinal severity. These findings suggest that CPJIP has the potential to serve as a promising candidate for the treatment of NEC.