A titratable murine model of progressive emphysema using tracheal porcine pancreatic elastase.
A titratable murine model of progressive emphysema using tracheal porcine pancreatic elastase.
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DOI：
10.1038/s41598-023-41527-1
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发表时间：
2023-09-14
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
进行性肺气肿常常导致终末期肺病。大多数肺气肿小鼠模型通常是适度的（即香烟烟雾暴露），并且随时间的变化难以量化。气管猪胰弹性蛋白酶模型（PPE）产生严重的损伤，但文献是矛盾的肺气肿是否改善，是稳定的，或随着时间的推移进展。我们假设有一个损伤阈值，低于这个阈值就会发生修复，高于这个阈值肺气肿就会稳定或进展。我们用溶于100 µL PBS中的0、0.5、2或4个活性单位PPE处理8周龄C57 BL 6混合性别小鼠，并在第21天和第84天时进行肺体视学检查。在体重增加或小鼠健康方面没有显著差异。尽管0.5单位组在第21天出现了轻微的肺气肿（平均线性截距增加2.8 µm，MLI），但在第21天和第84天之间，MLI增加了4.6 µm（p = 0.0007）。除了2单位组和4单位组在第21天的MLI较大外，第21天至第84天的MLI分别增加了17.2和34 µm（p = 0.002和p = 0.0001）。随着时间和损伤程度的增加，肺总容量增加，肺泡表面积减少。与我们的假设相反，我们没有发现牙槽骨修复随时间推移的证据。对领空的破坏是渐进的，也是加速的。未来在肺免疫、机械生物学、衰老和细胞特异性变化方面的机制研究可能会导致新的疗法来减缓或停止人类进行性肺气肿。
Progressive emphysema often leads to end-stage lung disease. Most mouse models of emphysema are typically modest (i.e. cigarette smoke exposure), and changes over time are difficult to quantify. The tracheal porcine pancreatic elastase model (PPE) produces severe injury, but the literature is conflicted as to whether emphysema improves, is stable, or progresses over time. We hypothesized a threshold of injury below which repair would occur and above which emphysema would be stable or progress. We treated 8-week-old C57BL6 mixed sex mice with 0, 0.5, 2, or 4 activity units of PPE in 100 µL PBS and performed lung stereology at 21 and 84 days. There were no significant differences in weight gain or mouse health. Despite minimal emphysema at 21-days in the 0.5 units group (2.8 µm increased mean linear intercept, MLI), MLI increased by 4.6 µm between days 21 and 84 (p = 0.0007). In addition to larger MLI at 21 days in 2- and 4-unit groups, MLI increases from day 21 to 84 were 17.2 and 34 µm respectively (p = 0.002 and p = 0.0001). Total lung volume increased, and alveolar surface area decreased with time and injury severity. Contrary to our hypothesis, we found no evidence of alveolar repair over time. Airspace destruction was both progressive and accelerative. Future mechanistic studies in lung immunity, mechano-biology, senescence, and cell-specific changes may lead to novel therapies to slow or halt progressive emphysema in humans.
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