Saadoun Ahmed Atef, Abdelsattar Alia Hamed, Elsaid Amro Hatem, Abdelaleam Eslam Abdelaziz, Abdelkader Hazem Khaled, Ibrahim Hend Mohamed, Saad Merna Sabri, Ellawi Moumen Said, Elsaid Rana Elshahawi, Maghrabia Aya, Ibrahim Dina, Ramadan Nehal M
Mansoura Manchester Medical Program, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Program of Medicine, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 5. doi: 10.1007/s00210-025-04339-w.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that typically requires long-term drug treatment. The emerging role of glucagon-like peptide 1 (GLP-1) and its receptor agonists in gastrointestinal diseases has drawn much attention. A mouse model of acute colitis was conducted using a 7-day protocol of dextran sulfate sodium (DSS, 3% w/v in drinking water) administration. The efficacy of liraglutide (a GLP-1 receptor agonist) in treating DSS-induced colitis and its accompanying Paneth cell metaplasia was examined and correlated to its impact on the levels of colonic autophagy. Liraglutide effectively ameliorated colitis symptoms in mice. Dose-dependent improvements in disease activity index (DAI), colon length, and histopathological scores of inflammation and mucosal damage were evident in the liraglutide-treated groups compared to the DSS group. In addition, liraglutide reduced the expression of lysozyme and suppressed colonic Paneth cell metaplasia induced by DSS. Notably, liraglutide also enhanced levels of colonic autophagy. Direct visualization of autophagosomes and autolysosomes under an electron microscope along with p62 accumulation following co-treatment with chloroquine supports the role of liraglutide as an autophagy enhancer. Liraglutide ameliorated DSS-induced colitis and prevented Paneth cell metaplasia possibly via enhancing colonic autophagy. Our findings strongly signify liraglutide as a therapeutic option for UC.
溃疡性结肠炎（UC）是一种慢性炎症性肠病（IBD），通常需要长期药物治疗。胰高血糖素样肽1（GLP-1）及其受体激动剂在胃肠道疾病中的新作用已引起广泛关注。使用葡聚糖硫酸钠（DSS，饮用水中3% w/v）给药7天的方案建立急性结肠炎小鼠模型。研究了利拉鲁肽（一种GLP-1受体激动剂）治疗DSS诱导的结肠炎及其伴随的潘氏细胞化生的疗效，并将其与对结肠自噬水平的影响相关联。利拉鲁肽有效改善了小鼠的结肠炎症状。与DSS组相比，利拉鲁肽治疗组的疾病活动指数（DAI）、结肠长度以及炎症和黏膜损伤的组织病理学评分呈剂量依赖性改善。此外，利拉鲁肽降低了溶菌酶的表达，并抑制了DSS诱导的结肠潘氏细胞化生。值得注意的是，利拉鲁肽还提高了结肠自噬水平。电子显微镜下自噬体和自溶酶体的直接可视化以及与氯喹共同处理后p62的积累支持了利拉鲁肽作为自噬增强剂的作用。利拉鲁肽可能通过增强结肠自噬改善DSS诱导的结肠炎并预防潘氏细胞化生。我们的研究结果有力地表明利拉鲁肽是UC的一种治疗选择。
