Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil.
Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil.
Sci Rep. 2024 Nov 20;14(1):28698. doi: 10.1038/s41598-024-80051-8.
Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies' adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. In this regard, omega-3 fatty acid-derived Resolvin D2 (RvD2) appears to play a protective role in the pathophysiology of IBD. Therefore, we characterized the RvD2 pathway and its receptor expression in the intestinal mucosa of experimental colitis induced by dextran sulfate sodium. We also evaluated the preventive impact of an omega-3-enriched diet and the therapeutic efficacy of RvD2 compared with anti-TNF-α treatment. We found an increase in TNFα and IL22 expression and decreased levels of enzymes involved in RvD2 biosynthesis, such as PLA, 15-LOX, 5-LOX, and its receptor GPR18 in experimental colitis. Omega-3 supplementation reduced the Disease Activity Index (DAI), weight loss, colonic shortening, and inflammation. These results and the increased IL-10 transcriptional levels after RvD2 treatment suggest that this mediator attenuated experimental colitis. These results enhance our understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in experimental colitis and suggest that RvD2 and its omega-3 precursor offer a promising therapeutic approach for IBD.
炎症性肠病（IBD）是一种特发性疾病，其特征为慢性胃肠道炎症。鉴于常规疗法的不良反应和临床失败，目前正在研究新的方法。最近的研究强调了专门的促解决脂质介质（SPM）在慢性炎症的主动解决中的作用。在这方面，ω-3 脂肪酸衍生的 Resolvin D2（RvD2）似乎在 IBD 的病理生理学中发挥保护作用。因此，我们在葡聚糖硫酸钠诱导的实验性结肠炎的肠黏膜中描述了 RvD2 途径及其受体表达。我们还评估了富含 ω-3 的饮食的预防作用以及与抗 TNF-α治疗相比 RvD2 的治疗效果。我们发现实验性结肠炎中 TNFα和 IL22 的表达增加，而 RvD2 生物合成相关酶的水平降低，例如 PLA、15-LOX、5-LOX 及其受体 GPR18。ω-3 补充剂可降低疾病活动指数（DAI）、体重减轻、结肠缩短和炎症。这些结果以及 RvD2 治疗后 IL-10 转录水平的增加表明该介质减轻了实验性结肠炎。这些结果增强了我们对实验性结肠炎中炎症反应加剧所涉及的分子机制的理解，并表明 RvD2 和其 ω-3 前体为 IBD 提供了一种有前途的治疗方法。
