Trudeau Institute, Saranac Lake, NY, 12983, USA.
Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Box 5810, Potsdam, NY, 13699, USA.
Adv Healthc Mater. 2017 Jul;6(14). doi: 10.1002/adhm.201700176. Epub 2017 May 8.
Accumulating evidence suggests that ischemia-reperfusion-induced injury is associated with the formation of reactive oxygen species (ROS). This study demonstrates the therapeutic effectiveness of novel europium-doped cerium oxide nanoparticles (Eu-doped Ceria NPs) as ROS scavengers in a mouse model of intestinal ischemia-reperfusion-induced injury. An increased production of superoxide radicals is detected in the intestine throughout the ischemia stage and again after initiating reperfusion. These changes in superoxide radical formation are associated with the induction of inflammatory cytokines in the intestine. This study further shows that Eu-Ceria NPs exhibit superoxide scavenging activity in vitro. Importantly, administration of Eu-Ceria NPs into the intestinal lumen during the onset of ischemia effectively blocks superoxide accumulation, reduces the expression of IL-1b, and ameliorates the intestinal pathology. These results suggest that early increased production of ROS during the ischemia-reperfusion promotes intestinal pathology and that mucosal delivery of Eu-Ceria NPs may be a potential therapeutic approach to block ROS accumulation and ameliorate the severity of intestinal disease.
越来越多的证据表明，缺血再灌注引起的损伤与活性氧（ROS）的形成有关。本研究证明了新型铕掺杂氧化铈纳米粒子（Eu 掺杂 Ceria NPs）作为 ROS 清除剂在肠缺血再灌注损伤小鼠模型中的治疗效果。在整个缺血阶段和再灌注开始后，肠道中超氧自由基的产生增加。这种超氧自由基形成的变化与肠道中炎症细胞因子的诱导有关。本研究进一步表明，Eu-Ceria NPs 在体外具有超氧自由基清除活性。重要的是，在缺血开始时将 Eu-Ceria NPs 注入肠腔可有效阻止超氧自由基的积累，降低 IL-1b 的表达，并改善肠道病理。这些结果表明，缺血再灌注过程中 ROS 的早期产生会促进肠道病理，而黏膜给予 Eu-Ceria NPs 可能是阻止 ROS 积累和改善肠道疾病严重程度的一种潜在治疗方法。
