Morin Caroline, Blier Pierre U, Fortin Samuel
SCF Pharma, Ste-Luce, Quebec, Canada; Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
Department of Biology, Université du Québec à Rimouski, Rimouski, Quebec, Canada.
Am J Physiol Gastrointest Liver Physiol. 2016 May 15;310(10):G808-21. doi: 10.1152/ajpgi.00136.2015. Epub 2016 Mar 24.
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats.
溃疡性结肠炎（UC）是一种以大肠肠黏膜弥漫性炎症为特征的慢性疾病。补充ω-3脂肪酸与参与UC发病机制的炎症细胞因子生成减少有关。本研究的目的是在葡聚糖硫酸钠（DSS）诱导的UC大鼠体内模型中确定二十碳五烯酸单甘油酯（MAG-EPA）的预防和治疗潜力。DSS大鼠未接受治疗或经口给予MAG-EPA。在给予MAG-EPA后进行形态学、组织学和生化分析。形态学和组织学分析显示，MAG-EPA预处理（DSS前12天）和治疗（DSS后6天）在减轻DSS大鼠疾病严重程度方面表现出强大活性。给予MAG-EPA后，与仅接受DSS治疗的大鼠相比，促炎细胞因子TNF-α、IL-1β和IL-6的组织水平显著降低。如髓过氧化物酶活性所示，经口给予MAG-EPA可减少结肠组织中的中性粒细胞浸润。结果还显示，在MAG-EPA预处理和治疗的大鼠的结肠匀浆中，NF-κB通路的激活减少，这与COX-2表达降低相关。对结肠组织进行的张力测量显示，MAG-EPA治疗后，对乙酰甲胆碱的收缩反应和硝普钠诱导的舒张作用大大增强。MAG-EPA与维生素E联合治疗对DSS大鼠中MAG-EPA的抗炎特性显示出拮抗作用。
