Inhibition of BTK protects lungs from trauma-hemorrhagic shock-induced injury in rats Corrigendum in /10.3892/mmr.2018.8625

Liu,Xinwei; Zhang,Jingdong; Han,Wenfeng; Wang,Yu; Liu,Yunen; Zhang,Yubiao; Zhou,Dapeng; Xiang,Liangbi

doi:10.3892/mmr.2017.6553

Inhibition of BTK protects lungs from trauma-hemorrhagic shock-induced injury in rats

Corrigendum in: /10.3892/mmr.2018.8625

Authors:
- Xinwei Liu
- Jingdong Zhang
- Wenfeng Han
- Yu Wang
- Yunen Liu
- Yubiao Zhang
- Dapeng Zhou
- Liangbi Xiang
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Affiliations: Department of Orthopaedic Surgery, Rescue Center for Severe Wound and Trauma of Chinese PLA, The General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, P.R. China, Laboratory of Severe and War‑Related Trauma Center, The General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, P.R. China
Published online on: May 9, 2017 https://doi.org/10.3892/mmr.2017.6553
Pages: 192-200
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role of Bruton's tyrosine kinase (BTK) in the pathogenesis of lung injury induced by trauma‑hemorrhagic shock (THS), and to examine the pulmonary protective effects of BTK inhibition. Male Sprague‑Dawley rats were divided into four groups (n=12/group): i) A Sham group, which received surgery without induced trauma; ii) a THS‑induced injury group; iii) a THS‑induced injury group that also received treatment with the BTK inhibitor LFM‑A13 prior to trauma induction; and iv) a Sham group that was pretreated with LFM‑A13 prior to surgery but did not receive induced trauma. The expression of phosphorylated‑BTK protein in the lungs was measured by immunohistochemistry and western blot analysis. The bronchoalveolar lavage fluid (BALF) protein concentration, total leukocyte and eosinophil numbers, and the expression levels of peripheral blood proinflammatory factors were measured. Morphological alterations in the lungs were detected by hematoxylin and eosin staining. Pulmonary nitric oxide (NO) concentration and inducible NO synthase (iNOS) expression were also assessed. Activities of the nuclear factor (NF)‑κB and mitogen‑activated protein kinase (MAPK) signaling pathways were determined by western blotting or electrophoretic mobility shift assay. BTK was notably activated in lungs of THS rats. BALF protein concentration, total leukocytes and eosinophils, peripheral blood expression levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and monocyte chemotactic protein 1 were significantly upregulated after THS induction, and each exhibited decreased expression upon LFM‑A13 treatment. THS‑induced interstitial hyperplasia, edema and neutrophilic infiltration in lungs were improved by the inhibition of BTK. In addition, THS‑induced NO release, iNOS overexpression, and NF‑κB and MAPK signaling were suppressed by BTK inhibition. Results from the present study demonstrate that BTK may serve a pivotal role in the pathogenesis of THS‑related lung injury, and the inhibition of BTK may significantly alleviate THS‑induced lung damage. These results provide a potential therapeutic application for the treatment of THS‑induced lung injury.

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