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Abstract：
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unknown pathogenesis which has been gradually considered a public health challenge worldwide. Peptides derived from Rapana venosa have been shown to have an anti-inflammatory effect. In this study, peptide LLTRAGL derived from Rapana venosa was prepared by a solid phase synthesis technique. The protective effects of LLTRAGL were studied in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced zebrafish colitis model. The underlying mechanisms of LLTRAGL were predicted and validated by transcriptome, real-time quantitative PCR assays and molecular docking. The results showed that LLTRAGL reduced the number of macrophages migrating to the intestine, enhanced the frequency and rate of intestinal peristalsis and improved intestinal inflammatory damage. Furthermore, transcriptome analysis indicated the key pathways (NOD-like receptor signal pathway and necroptosis pathway) that link the underlying protective effects of LLTRAGL\'s molecular mechanisms. In addition, the related genes in these pathways exhibited different expressions after TNBS treatment. Finally, molecular docking techniques further verified the RNA-sequencing results. In summary, LLTRAGL exerted protective effects in the model of TNBS-induced colitis zebrafish. Our findings provide valuable information for the future application of LLTRAGL in IBD.
摘要：
炎症性肠病(IBD)是一种发病机制不明的慢性炎症性肠病,已逐渐被认为是全球范围内的公共卫生挑战。衍生自Rapanavenosa的肽已显示具有抗炎作用。在这项研究中,通过固相合成技术制备源自Rapanavenosa的肽LLTRAGL。在2,4,6-三硝基苯磺酸（TNBS）诱导的斑马鱼结肠炎模型中研究了LLTRAGL的保护作用。通过转录组预测和验证了LLTRAGL的潜在机制，实时定量PCR检测和分子对接。结果显示，LLTRAGL减少了迁移到肠道的巨噬细胞的数量，提高肠蠕动的频率和速度，改善肠道炎症损伤。此外，转录组分析表明，关键途径（NOD样受体信号途径和坏死途径）连接了LLTRAGL分子机制的潜在保护作用。此外,这些通路中的相关基因在TNBS处理后表现出不同的表达。最后,分子对接技术进一步验证了RNA测序结果。总之,LLTRAGL在TNBS诱导的结肠炎斑马鱼模型中发挥保护作用。我们的发现为未来LLTRAGL在IBD中的应用提供了有价值的信息。
