Autoimmunity & Immune Regulation (AIR), Department of Clinical & Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Institute, Balanagar, Hyderabad, 500037, India.
Sci Rep. 2017 Jun 20;7(1):3924. doi: 10.1038/s41598-017-04041-9.
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily. Uridine at medium and high dose significantly reduced the severity of colitis (DAI score) and alleviated the macroscopic and microscopic signs of the disease. The levels of proinflammatory cytokines IL-6, IL-1β and TNF in serum as well as mRNA expression in colon were significantly reduced in the uridine treated groups. Moreover, colon tissue myloperoxidase activities, protein expression of IL-6, TNF- α, COX-2, P-NFkB and P-Ikk-βα in the colon tissues were significantly reduced in medium and high dose groups. These findings demonstrated that local administration of uridine alleviated experimental colitis in male C57BL/6 mice accompanied by the inhibition of neutrophil infiltration and NF-κB signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.
尿苷，RNA 的四个组成部分之一，作为一种新型的炎症治疗调节剂引起了人们的关注。然而，人们对其在肠道炎症中的作用知之甚少。本研究旨在探讨经结肠内给予尿苷对雄性 C57BL/6 小鼠 DSS 诱导结肠炎的潜在保护作用。每日用生理盐水对结肠内给予 3 剂量的尿苷 1mg/Kg（低剂量）、5mg/Kg（中剂量）和 10mg/Kg（高剂量）。中剂量和高剂量的尿苷可显著减轻结肠炎的严重程度（DAI 评分），并缓解疾病的宏观和微观征象。尿苷治疗组血清中促炎细胞因子 IL-6、IL-1β 和 TNF 的水平以及结肠中 mRNA 的表达均显著降低。此外，中剂量和高剂量组结肠组织髓过氧化物酶活性、IL-6、TNF-α、COX-2、P-NFkB 和 P-Ikk-βα 的蛋白表达在结肠组织中均显著降低。这些发现表明，局部给予尿苷可缓解雄性 C57BL/6 小鼠实验性结肠炎，同时抑制中性粒细胞浸润和 NF-κB 信号转导。因此，尿苷可能是未来治疗炎症性肠病的有前途的候选药物。
