CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model

被引:11
|
作者
Wallbank, Alison M. [1 ]
Vaughn, Alyssa E. [2 ]
Niemiec, Steve [2 ]
Bilodeaux, Jill [1 ]
Lehmann, Tanner [2 ]
Knudsen, Lars [3 ,4 ]
Kolanthai, Elayaraja [5 ]
Seal, Sudipta [5 ]
Zgheib, Carlos [2 ,6 ,7 ]
Nozik, Eva [8 ,9 ]
Liechty, Kenneth W. [2 ,6 ,7 ]
Smith, Bradford J. [1 ,10 ]
机构
[1] Univ Colorado Denver, Dept Bioengn, Anschutz Med Campus,12705 E Montview Blvd,Suite 1, Aurora, CO 80045 USA
[2] Univ Colorado, Denver Sch Med, Childrens Hosp Colorado, Dept Surg,Lab Fetal & Regenerat Biol, Aurora, CO USA
[3] German Ctr Lung Res DZL, Biomed Res Endstage & Obstructive Lung Dis Hannov, Hannover, Germany
[4] German Ctr Lung Res, Biomed Res Endstage & Obstructive Lung Dis Hannov, Hannover, Germany
[5] Univ Cent Florida, Adv Mat Proc & Anal Ctr, Dept Mat Sci & Engn, Orlando, FL USA
[6] Univ Arizona Tucson, Coll Med, Dept Surg, Lab Fetal & Regenerat Biol, Tucson, AZ USA
[7] Banner Childrens Diamond Childrens Med Ctr, Tucson, AZ USA
[8] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Div Pediat Crit Care,Cardiovasc Pulm Res Labs,Dev, Aurora, CO USA
[9] Univ Colorado, Dept Pediat, Div Pulm Sci & Crit Care Med, Div Pediat Crit Care,Cardiovasc Pulm Res Labs,Dev, Aurora, CO USA
[10] Univ Colorado, Sch Med, Dept Pediat Pulm & Sleep Med, Aurora, CO USA
关键词
Bioactive nanoparticle therapeutic; Ventilator-induced lung injury; Stereology; Sterile inflammatory model; CARE;
D O I
10.1016/j.nano.2023.102679
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Acute respiratory distress syndrome (ARDS) has high mortality (similar to 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 bio-markers, 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. (C) 2023 Elsevier Inc. All rights reserved.y
引用
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页数:12
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