CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model.
CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model.
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CNP-miR 146 a改善了两次打击急性和呼吸机诱导的肺损伤模型的结果。
DOI：
10.1016/j.nano.2023.102679
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发表时间：
2023-06
影响因子：
5.4
通讯作者：
Smith, Bradford J.
中科院分区：
文献类型：
--
作者：
Wallbank, Alison M.;Vaughn, Alyssa E.;Niemiec, Steve;Bilodeaux, Jill;Lehmann, Tanner;Knudsen, Lars;Kolanthai, Elayaraja;Seal, Sudipta;Zgheib, Carlos;Nozik, Eva;Liechty, Kenneth W.;Smith, Bradford J.
关键词：
急性呼吸窘迫综合征(ARDS)病死率高(~40%)，需要机械通气的救命干预。各种全身性炎性损伤可进展为ARDS，炎症和损伤的肺对呼吸机诱导的肺损伤(VILI)易感。在恢复肺功能的同时减轻炎症反应的策略是有限的，因此我们试图确定CNP-miR146a是否能保护小鼠肺免受气管内毒素诱导的急性肺损伤(ALI)和随后的VILI。CNP-miR146a是新型自由基清除氧化铈纳米颗粒(CNP)和抗炎microRNA(MiR)-146a的结合物。通过肺机械功能、炎症生物标志物相关基因表达和肺形态计量学(体视学)评价肺损伤程度和治疗效果。CNP-miR146a减轻了ALI的严重程度，减缓了VILI的进展，表现为炎症生物标志物、肺不张、实质空气中的气量和肺系统僵硬的改善。目前还没有治疗急性呼吸窘迫综合征的药物，治疗的中心是挽救生命的机械通气，但这种干预可能会导致呼吸机诱发的肺损伤和更糟糕的结果。我们的研究利用模拟肺损伤和呼吸的临床过程的两次打击小鼠肺损伤模型来测试与抗炎微RNA(MiR146a)结合的氧化铈纳米颗粒(CNPs)的治疗效果。我们发现，治疗性的CNP-miR146a可以减少炎症，防止肺不张，恢复机械功能，并保护预先受伤的肺免受呼吸机诱导的肺损伤。
Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system. There are no pharmaceutical treatments for acute respiratory distress syndrome and management is centered on life-saving mechanical ventilation, but that intervention can cause ventilator-induced lung injury and worse outcomes. Our study utilizes a two-hit murine lung injury model that emulates the clinical course of lung injury and ventilation to test the therapeutic efficacy of cerium oxide nanoparticles (CNPs) conjugated to an anti-inflammatory micro RNA (miR146a). We found the therapeutic, CNP-miR146a, reduced inflammation, prevented atelectasis, restored mechanical function, and protected pre-injured lungs from ventilator-induced lung injury.
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DOI：
10.1016/j.nano.2021.102498
发表时间：
2022-03
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
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
通讯作者：
Liechty KW
影响因子：
39.3
作者：
Liu T;Zhang L;Joo D;Sun SC
通讯作者：
Sun SC
影响因子：
2.7
作者：
Benjamini, Yoav;Krieger, Abba M.;Yekutieli, Daniel
通讯作者：
Yekutieli, Daniel
影响因子：
39
作者：
Wu, Chaomin;Chen, Xiaoyan;Song, Yuanlin
通讯作者：
Song, Yuanlin
影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.