Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

Hu,Quan; Wang,Qin; Han,Chuangang; Yang,Yan

doi:10.3892/mmr.2020.11526

Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

Authors:
- Quan Hu
- Qin Wang
- Chuangang Han
- Yan Yang
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Affiliations: Intensive Care Unit, The First People's Hospital, Wuhan, Hubei 430200, P.R. China, Department of Pathology, Hubei Women and Children Health Care Hospital, Wuhan, Hubei 430200, P.R. China, Department of Anesthesiology, The First People's Hospital, Wuhan, Hubei 430200, P.R. China
Published online on: September 18, 2020 https://doi.org/10.3892/mmr.2020.11526
Pages: 4298-4306
Copyright: © Hu 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 effects of sufentanil on sepsis-induced acute lung injury (ALI), and identify the potential molecular mechanisms underlying its effect. In order to achieve this, a rat sepsis model was established. Following treatment with sufentanil, the lung wet/dry (W/D) weight ratio was calculated. Histopathological analysis was performed via hematoxylin and eosin staining. Levels of inflammatory factors in bronchoalveolar lavage fluid were determined via ELISA. Furthermore, malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in tissue homogenates were assessed using commercial kits. Western blot analysis was performed to determine kininogen-1 (KNG1) protein expression. In addition, alveolar epithelial type II cells (AEC II) were stimulated with lipopolysaccharide (LPS) to mimic ALI. The levels of inflammation and oxidative stress were evaluated following overexpression of KNG1. Protein expression levels of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling were determined via western blot analysis. The results of the present study demonstrated that sufentanil alleviated histopathological injury and the W/D ratio in lung tissue. Following treatment with sufentanil, levels of inflammatory factors also decreased, accompanied by decreased concentrations of MDA, and increased activities of SOD, CAT and GSH-Px. Notably, KNG1 was decreased in lung tissues following treatment with sufentanil. Furthermore, overexpression of KNG1 attenuated the inhibitory effects of sufentanil on LPS-induced inflammation and oxidative stress in AEC II. Sufentanil markedly downregulated NF-κB expression, while upregulating Nrf2 and HO-1 expression levels, which was reversed following overexpression of KNG1. Taken together, the results of the present study suggested that sufentanil may alleviate inflammation and oxidative stress in sepsis-induced ALI by downregulating KNG1 expression.

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