Department of Hepatopancreatobiliary Medicine, Digestive Diseases Center, The Second Hospital, Jilin University, Changchun 130000, PR China.
Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130000, PR China.
Aging (Albany NY). 2023 Aug 17;15(16):8044-8060. doi: 10.18632/aging.204953.
Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. The incidence and prevalence of UC is increasing worldwide. The global burden of UC, which can substantially reduce quality of life, is clearly increasing. These data highlight the need for research into prevention of UC and innovations in health-care systems to manage this complex and costly disease. Glucagon-like peptide-1 (GLP-1), a new antidiabetic drug, is used to treat Type 2 Diabetes Mellitus (T2DM). Accumulating evidence suggests that GLP-1 has additional roles other than glucose-lowering effects. Despite the abundance of GLP-1 research, studies in UC have been less consistent, especially body weight; for example, body weight, colon length, colon injury score, intestinal microbiota, remain to be studied further. To date, the molecular mechanism of the protective effect of GLP-1 on UC remains obscure. The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under and conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC.
溃疡性结肠炎(UC)是一种主要的结肠黏膜慢性炎症性肠病,具有进行性发病的特点。UC 的发病率和患病率在全球范围内呈上升趋势。UC 的全球负担明显增加,这会极大地降低生活质量。这些数据突出表明,需要研究 UC 的预防措施,并创新医疗保健系统来管理这种复杂且昂贵的疾病。胰高血糖素样肽-1(GLP-1)是一种新型的抗糖尿病药物,用于治疗 2 型糖尿病(T2DM)。越来越多的证据表明,GLP-1 除了具有降低血糖的作用外,还有其他作用。尽管对 GLP-1 进行了大量研究,但在 UC 中的研究结果并不一致,特别是体重方面;例如,体重、结肠长度、结肠损伤评分、肠道微生物群等仍需进一步研究。迄今为止,GLP-1 对 UC 的保护作用的分子机制仍不清楚。本研究分别采用葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠和脂多糖(LPS)处理的 RAW264.7 细胞(巨噬细胞系)来研究 GLP-1 的作用。结果表明,GLP-1 通过抑制促炎介质的产生,显著缓解溃疡性结肠炎。此外,GLP-1 阻断蛋白激酶 B(AKT)/核因子-κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路的激活。GLP-1 还减轻 DSS 诱导的肠黏膜损伤和肠道微生物群失调。总之,GLP-1 对溃疡性结肠炎具有保护作用。因此,GLP-1 可以被认为是治疗 UC 的一种有潜力的治疗候选药物。