JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?

Author(s): Yu Zhao¹, Chong-wei Zhang¹, Wen-jing Zhou¹, Jiao Chen¹, Nan-fu Luo², Li-na Gong², Lei Du², Jing Zhou¹
Affiliation(s): 1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;2. Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China
Corresponding email(s): zhoujinghuaxi@163.com
Key Words: Extracorporeal circulation (ECC), Acute lung injury (ALI), Tumor necrosis factor receptor 1 (TNFR1), Tumor necrosis factor- (TNF-)

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Yu Zhao, Chong-wei Zhang, Wen-jing Zhou, Jiao Chen, Nan-fu Luo, Li-na Gong, Lei Du, Jing Zhou. Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B1300147

@article{title="Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?",
author="Yu Zhao, Chong-wei Zhang, Wen-jing Zhou, Jiao Chen, Nan-fu Luo, Li-na Gong, Lei Du, Jing Zhou",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B1300147"
}

%0 Journal Article
%T Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?
%A Yu Zhao
%A Chong-wei Zhang
%A Wen-jing Zhou
%A Jiao Chen
%A Nan-fu Luo
%A Li-na Gong
%A Lei Du
%A Jing Zhou
%J Journal of Zhejiang University SCIENCE B
%P 281-288
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B1300147"

TY - JOUR
T1 - Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?
A1 - Yu Zhao
A1 - Chong-wei Zhang
A1 - Wen-jing Zhou
A1 - Jiao Chen
A1 - Nan-fu Luo
A1 - Li-na Gong
A1 - Lei Du
A1 - Jing Zhou
J0 - Journal of Zhejiang University Science B
SP - 281
EP - 288
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B1300147"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.

肿瘤坏死因子受体1是否在体外循环相关的急性肺损伤病例中发挥作用？

研究目的：通过CAY10500阻断肿瘤坏死因子-α（TNF-α）与肿瘤坏死因子受体1（TNFR1）的结合，评估TNFR1在体外循环诱导的急性肺损伤中的作用。
创新要点：使用CAY10500静脉内注射预处理而阻断TNF-α与TNFR1的结合，并降低血浆TNF-α水平，以观察TNFR1对体外循环诱导的急性肺损伤的作用。
研究方法：用磷酸盐缓冲液（PBS）或载体或CAY10500静脉内预处理麻醉SD大鼠后，再进行2小时体外循环，诱导其发生急性肺损伤，并观察氧指数、肺部炎症、支气管肺泡灌洗液及其血浆中TNF-α和嗜中性粒细胞的含量。
重要结论：使用CAY10500静脉内注射预处理而阻断TNF-α与TNFR1的结合，只能略微减轻肺部炎症，但不能改善肺部功能，表明TNFR1通路在体外循环诱导的急性肺损伤的炎症细胞中作用有限。

关键词组：体外循环；急性肺损伤；肿瘤坏死因子受体1；肿瘤坏死因子-α

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肿瘤坏死因子受体1是否在体外循环相关的急性肺损伤病例中发挥作用？

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References