生物催化簇酶贴片通过免疫调节和线粒体保护恢复肺功能

Wei Liu, Sufei Zhou, Ke Yang, Di Liu, Yuxing Yan, Fangzhen Tian, Tianyi Cui, Wei Wang, Lewei Bi, Lan Li, Hao Wang, Xiao-Dong Zhang
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摘要

目前,由于缺乏有效药物,围术期肺部感染等肺部并发症仍是肺损伤患者住院时间延长和死亡的主要原因。集束酶是一种具有高酶样活性和安全性的人工酶,在降低氧化应激和免疫调节方面具有良好的效果。在这里,我们展示了一种功能化贴片,它可以贴在肺部气管上,通过聚类酶来挽救受伤器官。贴片的长期抗氧化能力能明显改善脂多糖引起的肺功能损伤,显著减少肺小泡细胞增生和氧化应激。白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α等细胞因子水平下降了50%,而mtDNA拷贝数增加了50%,ATP生成增加了100%。小鼠肺功能明显改善,表明贴片可通过调节氧化应激和免疫反应以及保护线粒体来挽救肺损伤,为有效干预肺损伤提供了途径。
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Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection
Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.
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