Netrin-1 Dampens Hypobaric Hypoxia-Induced Lung Injury in Mice

Ching Lung Ko, Jui An Lin, Kung Yen Chen, An Chih Hsu, Shu Yu Wu, Yu Ting Tai, Ko Huan Lin, Wei Chen Chung, Min Hui Li

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Background: This study aimed to explore the effects of netrin-1 on hypobaric hypoxia-induced lung injury in mice. Methods: We exposed 6-8-week-old C57BL/6 mice to hypobaric stress at 340 mmHg for 30 minutes followed by 260 mmHg for different periods (6, 12, 18, and 24 hours) to observe the severity of lung injury (O2 concentration, 21%; 54.6 mmHg). The wet/dry weight ratio and protein leakage from the mouse lung were used to determine the suitable exposure time. Netrin-1 was injected into the tail vein of mice before 18-hour decompression. Inflammatory cytokines, lung injury scores, and activity of nuclear factor κB were evaluated. The expression of apoptosis-related proteins was also examined. Results: Protein concentration in the bronchoalveolar lavage fluid was significantly higher in the 18-hour group (p < 0.05). Pulmonary pathology revealed neutrophil infiltration, alveolar septum thickening, and tissue edema. Injury score and macrophage inflammatory protein 2 levels were also increased. Intrinsic apoptosis pathway was activated. Hypoxia decreased the expression of Bcl2 protein, the number of active caspase-3-stained cells, and UNC5HB receptors. Pretreatment with netrin-1 reduced protein leakage, inhibited neutrophil migration, lowered the injury score, attenuated apoptosis, and increased UNC5HB receptor expression. Conclusion: Netrin-1 dampens hypobaric hypoxia-induced lung injury by inhibiting neutrophil migration and attenuating apoptosis.
原文英語
頁(從 - 到)293-302
頁數10
期刊High Altitude Medicine and Biology
20
發行號3
DOIs
出版狀態已發佈 - 九月 2019

ASJC Scopus subject areas

  • 生理學
  • 公共衛生、環境和職業健康

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