Age-Dependent Chronic Lung Injury and Pulmonary Fibrosis following Single Exposure to Hydrochloric Acid.
Age-Dependent Chronic Lung Injury and Pulmonary Fibrosis following Single Exposure to Hydrochloric Acid.
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DOI：
10.3390/ijms22168833
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发表时间：
2021-08-17
影响因子：
5.6
通讯作者：
Catravas JD
中科院分区：
文献类型：
--
作者：
Colunga Biancatelli RML;Solopov P;Dimitropoulou C;Catravas JD
暴露于盐酸（HCl）对公众健康构成威胁。儿童可能吸入更高的剂量，并发展更大的伤害，因为他们的气道较小和呼吸频率较快。我们通过向p24小鼠（小鼠24日龄; 8-10 g）气管内滴注2 µL/g 0.1 N HCl，建立了儿童暴露于HCl的小鼠模型，并将肺损伤特征与盐酸滴注成人（10周龄; 25-30 g）及其年龄匹配的生理盐水对照进行了比较。30天后，观察到肺泡炎症与增加的蛋白质沉积和单核细胞的支气管肺泡灌洗液（BALF）中的盐酸滴注组。年轻的p24动物，但不是成年人，表现出较高的NLR家族pyrin结构域3（NLRP 3）炎性小体水平。在年轻和成年HCl灌注小鼠的肺中发现转化生长因子-β（TGF-β）mRNA及其细胞内经典和非经典途径（p-Smad 2和p-ERK）的量增加。热休克蛋白家族（HSP 70和HSP 90）的表达水平存在年龄相关的组成性差异。盐酸同样引起胶原蛋白和纤连蛋白的沉积，然而，显着的年龄依赖性差异，观察到弹性蛋白和腱生蛋白C mRNA的增加。盐酸诱导肺纤维化，Ashcroft评分增加，成人更高，肺泡平均肺泡线性截距（MALI）降低。幼龄小鼠的牛顿阻力（Rn）增加，PV环降低，而成年小鼠的呼吸系统阻力和弹性较高。这些数据表明，年轻的p24小鼠可能因单次暴露于HCl而遭受长期并发症，并且可能发展出慢性肺损伤，其特征在于更强的持续性炎症和更少的纤维化模式，主要在气道中，与成年人不同。需要进一步的数据来表征年幼动物中盐酸时间和剂量依赖性损伤，并确定新的关键分子靶点。
Exposure to hydrochloric acid (HCl) represents a threat to public health. Children may inhale higher doses and develop greater injury because of their smaller airways and faster respiratory rate. We have developed a mouse model of pediatric exposure to HCl by intratracheally instilling p24 mice (mice 24 days old; 8–10 g) with 2 µL/g 0.1 N HCl, and compared the profile of lung injury to that in HCl-instilled adults (10 weeks old; 25–30 g) and their age-matched saline controls. After 30 days, alveolar inflammation was observed with increased proteinosis and mononuclear cells in the bronchoalveolar lavage fluid (BALF) in both HCl-instilled groups. Young p24 animals—but not adults—exhibited higher NLR family pyrin domain containing 3 (NLRP3) inflammasome levels. Increased amounts of Transforming Growth Factor-β (TGF-β) mRNA and its intracellular canonical and non-canonical pathways (p-Smad2 and p-ERK) were found in the lungs of both young and adult HCl-instilled mice. Constitutive age-related differences were observed in the levels of heat shock protein family (HSP70 and HSP90). HCl equally provoked the deposition of collagen and fibronectin; however, significant age-dependent differences were observed in the increase in elastin and tenascin C mRNA. HCl induced pulmonary fibrosis with an increased Ashcroft score, which was higher in adults, and a reduction in alveolar Mean Alveolar Linear Intercept (MALI). Young mice developed increased Newtonian resistance (Rn) and lower PV loops, while adults showed a higher respiratory system resistance and elastance. This data indicate that young p24 mice can suffer long-term complications from a single exposure to HCl, and can develop chronic lung injury characterized by a stronger persistent inflammation and lesser fibrotic pattern, mostly in the airways, differently from adults. Further data are required to characterize HCl time- and dose-dependent injury in young animals and to identify new key-molecular targets.
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影响因子：
3.1
作者：
Crowley, George;Kwon, Sophia;Nolan, Anna
通讯作者：
Nolan, Anna
DOI：
10.1158/1078-0432.ccr-16-3151
发表时间：
2017-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
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Puduvalli VK
DOI：
10.1164/rccm.201403-0509pp
发表时间：
2014-10-15
影响因子：
24.7
作者：
Ahluwalia, Neil;Shea, Barry S.;Tager, Andrew M.
通讯作者：
Tager, Andrew M.
DOI：
10.2174/1874312901206010080
发表时间：
2012
期刊：
The open rheumatology journal
影响因子：
--
作者：
Artlett CM
通讯作者：
Artlett CM
影响因子：
9.6
作者：
BROOKS, SM;WEISS, MA;BERNSTEIN, IL
通讯作者：
BERNSTEIN, IL