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Journal of Anesthesia
Published in: Journal of Anesthesia 3/2021

01-06-2021 | Acute Respiratory Distress-Syndrome | Original Article

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

Authors: Haibin Cui, Qian Zhang

Published in: Journal of Anesthesia | Issue 3/2021

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Abstract

Purpose

Dexmedetomidine (DEX) has been associated with inflammation, oxidative stress, and apoptosis, but its effects on lipopolysaccharide (LPS)-induced lung injury remain uncertain. The present study explored the effects of DEX on LPS-induced lung injury and studied the possible molecular mechanisms by testing the effects of the phosphoinositide-3 kinase (PI3K) inhibitor LY294002 and BEZ235.

Methods

Seventy C57BL/6 mice were randomly divided into the control, LPS, LPS + DEX, LPS + LY294002, LPS + BEZ235, LPS + DEX + LY294002, and LPS + DEX + BEZ235groups. Lung samples were collected 48 h after LPS treatment.

Results

DEX significantly inhibited LPS-induced increases in the lung weight/body weight ratio and lung wet/dry weight ratio, decreased inflammatory cell infiltration, and decreased the production of proinflammatory factors, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)in the lungs. DEX also markedly attenuated the increases in malondialdehyde 5 (MDA 5) and inositol-dependent enzyme a (IRE-a), attenuated the decrease in superoxide dismutase 1(SOD-1), reversed the low expression of B-cell lymphoma-2 (Bcl-2), and the high expressions of Bax and Caspase-3. DEX also decreased the expression of phosphorylated PI3K and phosphorylated Akt and increased the expression of phosphorylated forkhead box-O transcription factor 1 (FoxO1). More interestingly, LY294002 or BEZ235 pretreatment significantly abolished the inhibitory effects of DEX on LPS-induced lung inflammation, oxidative stress, and apoptosis.

Conclusions

These data suggest that DEX ameliorates LPS-induced acute lung injury partly through the PI3K/Akt/FoxO1 signaling pathway.
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Metadata
Title
Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway
Authors
Haibin Cui
Qian Zhang
Publication date
01-06-2021
Publisher
Springer Singapore
Published in
Journal of Anesthesia / Issue 3/2021
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-021-02909-9

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