Lung function improves after delayed treatment with CNP-miR146a following acute lung injury.
Lung function improves after delayed treatment with CNP-miR146a following acute lung injury.
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DOI：
10.1016/j.nano.2021.102498
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Liechty KW
中科院分区：
文献类型：
--
作者：
Niemiec SM;Hilton SA;Wallbank A;Louiselle AE;Elajaili H;Hu J;Singh S;Seal S;Nozik E;Smith B;Zgheib C;Liechty KW
急性呼吸窘迫综合征(ARDS)是一种以缺氧性呼吸衰竭为特征的高度发病率的肺部疾病。其发病机制以不受抑制的氧化应激和炎症反应为特征，并伴有肺纤维化和肺功能减退的长期后遗症。不幸的是，先前的ARDS治疗性试验都失败了，治疗仅限于支持性措施。自由基清除氧化铈纳米颗粒(CNP)与抗炎microRNA-146a(MiR146a)结合，被称为CNP-miR146a，已被证明在临床前模型中可以预防急性肺损伤。在这项研究中，我们评估了在损伤后三天或七天使用CNP-miR146a延迟治疗以从急性损伤中拯救肺的可能性。我们发现，伤后3天气管内注射CNP-miR146a可减少肺内白细胞的浸润，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。博莱霉素诱导的肺损伤引发急性炎症反应，白细胞募集增加，氧化应激增加。这种急性损伤以纤维化和肺功能受损的形式导致病理重塑。损伤发生三天后，CNP-miR146a气管内给药，氧化铈纳米颗粒(CNP)与microRNA-146的偶联，将肺部从炎症和氧化应激损伤中拯救出来，降低纤维化，最终改善肺功能。
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. Bleomycin-induced lung injury initiates an acute inflammatory response with higher leukocyte recruitment and increased oxidative stress. This acute injury leads to pathologic remodeling in the form of fibrosis and impaired pulmonary function. Intratracheal delivery of CNP-miR146a, the conjugation of cerium oxide nanoparticles (CNP) to microRNA-146, three days after onset of injury rescues the lungs from this inflammatory and oxidative stress injury, lowering fibrosis and ultimately improving lung function.
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影响因子：
4.1
作者：
Griffiths, Mark J. D.;McAuley, Danny Francis;Baudouin, Simon V.
通讯作者：
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影响因子：
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An R;Feng J;Xi C;Xu J;Sun L
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影响因子：
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作者：
Heckert, Eric G.;Karakoti, Ajay S.;Self, William T.
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DOI：
10.1164/rccm.202009-3536oc
发表时间：
2021-06-01
影响因子：
24.7
作者：
Goligher, Ewan C.;Costa, Eduardo L., V;Amato, Marcelo P. B.
通讯作者：
Amato, Marcelo P. B.
影响因子：
19.7
作者：
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