Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, USA.
Nanomedicine. 2022 Feb;40:102498. doi: 10.1016/j.nano.2021.102498. Epub 2021 Nov 26.
Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and therapy is limited to supportive measures. Free radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA-146a (miR146a), termed CNP-miR146a, have been shown to prevent acute lung injury in a pre-clinical model. In this study, we evaluated the potential of delayed treatment with CNP-miR146a at three or seven days after injury to rescue the lung from acute injury. We found that intratracheal CNP-miR146a administered three days after injury lowers pulmonary leukocyte infiltration, reduce inflammation and oxidative stress, lower pro-fibrotic gene expression and collagen deposition in the lung, and ultimately improve pulmonary function.
急性呼吸窘迫综合征（ARDS）是一种以低氧性呼吸衰竭为特征的高病死率肺部疾病。其发病机制以不受控制的氧化应激和炎症为特征，长期后果为肺纤维化和肺功能下降。不幸的是，先前的治疗 ARDS 的试验均以失败告终，治疗仅限于支持性措施。已证明与抗炎 microRNA-146a（miR146a）偶联的自由基清除铈氧化物纳米颗粒（CNP），称为 CNP-miR146a，可预防临床前模型中的急性肺损伤。在这项研究中，我们评估了在损伤后 3 天或 7 天给予 CNP-miR146a 延迟治疗以从急性损伤中挽救肺部的潜力。我们发现，损伤后 3 天给予气管内 CNP-miR146a 可降低肺白细胞浸润，减轻炎症和氧化应激，降低肺内促纤维化基因表达和胶原沉积，最终改善肺功能。
