Maresin 1 alleviates dextran sulfate sodium-induced ulcerative colitis by regulating NRF2 and TLR4/NF-kB signaling pathway
Maresin 1 alleviates dextran sulfate sodium-induced ulcerative colitis by regulating NRF2 and TLR4/NF-kB signaling pathway
复制标题
maresin 1通过调控NRF2以及TLR4/NF-κB信号通路缓解葡聚糖硫酸钠诱导的溃疡性结肠炎
DOI：
10.1016/j.intimp.2019.106018
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Li, Xiaofang
中科院分区：
文献类型：
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作者：
Qiu, Shujin;Li, Ping;Li, Xiaofang
目的：溃疡性结肠炎（UC）是最常见的胃肠道疾病之一，其特点是慢性、复发性炎症，导致结肠粘膜损伤。marsin 1 （MaR1）是一种特殊的促炎性介质，具有强大的抗炎活性，可预防各种炎症性疾病的发生。本研究旨在探讨MaR1在dss诱导的溃疡性结肠炎中的作用及其潜在机制。方法：建立葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎大鼠体内模型。结肠炎大鼠尾静脉注射MaR1，腹腔注射或不注射ML385。分析大鼠体重、结肠长度、疾病活动指数（DAI）、结肠组织病理学、炎症因子、髓过氧化物酶（MPO）和活性氧（ROS）活性以及表达F4/80的巨噬细胞浸润的变化，评价结肠炎严重程度。western blot检测蛋白表达。结果：MaR1显著降低炎症细胞因子的产生，恢复体重、DAI和结肠组织病理学。此外，MaR1提高了TJ蛋白的表达，减少了中性粒细胞和巨噬细胞的浸润，降低了MPO和ROS的活性。同时，MaR1激活Nrf2信号，降低toll样受体4(TLR4)/核因子κ B（nf - κ B）的激活。此外，Nrf2抑制剂ML385显著逆转了MaR1的保护作用。结论：MaR1通过激活Nrf2信号通路，灭活Nrf2介导的TLR4/NF-kappa B信号通路，介导大鼠促炎介质和肠道TJ蛋白，在dss诱导的结肠炎中发挥保护作用，为结肠炎的治疗策略提供新的见解。
Objective: Ulcerative colitis (UC) is one of the most common gastrointestinal diseases, characterized as a chronic, relapsing inflammation that causes damage to the colonic mucosa. Maresin 1 (MaR1), a specialized proresolving mediator, has powerful anti-inflammatory activity that prevents the occurrence of various inflammatory diseases. The aim of this study was to explore the role and potential mechanism of MaR1 in DSS-induced ulcerative colitis.Methods: In the present study, we established dextran sulfate sodium (DSS)-induced ulcerative colitis rat model in vivo. Rats with colitis received tail vein injection of MaR1, with or without intraperitoneal injection of ML385. The changes of body weight, colon length, disease activity index (DAI), colonic histopathology, inflammatory cytokines, the activity of myeloperoxidase (MPO) and reactive oxygen species (ROS), and infiltration of macrophages expressing F4/80 were analyzed for the evaluation of colitis severity. In addition, protein expressions were detected using western blot.Results: MaR1 significantly reduced inflammatory cytokines production, and restored body weight, DAI and colonic histopathology. Besides, MaR1 improved the expression of tight junction (TJ) proteins and reduced the infiltration of neutrophil and macrophages, as well as a decreased activity of MPO and ROS. Meanwhile, MaR1 activated Nrf2 signaling and decreased toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-kappa B) activation. Furthermore, ML385, an inhibitor of Nrf2, significantly reversed the protective effect of MaR1.Conclusion: MaR1 play a protective role in DSS-induced colitis by activating Nrf2 signaling and inactivating Nrf2-mediated TLR4/NF-kappa B signaling pathway, which mediate proinflammatory mediators and intestinal TJ proteins in rats, providing novel insights into the therapeutic strategy of colitis.