Dexmedetomidine reduces ventilator-induced lung injury -[kappa]B signaling pathway

Mechanical ventilation (MV) may lead to ventilator-induced lung injury (VILI). Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against...

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Published in:Bosnian journal of basic medical sciences 2018-05, Vol.18 (2), p.162
Main Authors: Chen, Hongli, Sun, Xiaotong, Yang, Xiaomei, Hou, Yonghao, Yu, Xiaoqian, Wang, Yang, Wu, Jianbo, Liu, Dejie, Wang, Huanliang, Yu, Jingui, Yi, Wenbo
Format: Article
Language:English
Subjects:
Artificial respiration
Cellular signal transduction
Complications and side effects
Dexmedetomidine
Drug therapy
Health aspects
Inflammation
Prevention
Respiratory insufficiency
Risk factors
Testing
TLR4
Transcription factors
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Summary:Mechanical ventilation (MV) may lead to ventilator-induced lung injury (VILI). Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against VILI and to explore the possible molecular mechanisms using the rat model. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to 5 groups (n = 6): control, low tidal volume MV (LMV), high tidal volume (H[V.sub.T]) MV (HMV), H[V.sub.T] MV + dexmedetomidine (DEX), H[V.sub.T] MV + dexmedetomidine + yohimbine (DEX+Y). Rats were euthanized after being ventilated for 4 hours. Pathological changes, lung wet/dry (W/D) weight ratio, lung myeloperoxidase (MPO) activity, levels of inflammatory cytokines (i.e., interleukin [IL]-1[beta], tumor necrosis factor alpha [TNF-[alpha]], and IL-6) in the bronchoalveolar lavage fluid (BALF) and lung tissues, expression of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-[kappa]B, and activation of NF-[kappa]B in lung tissues were measured. Compared with HMV, DEX group showed fewer pathological changes, lower W/D ratios and decreased MPO activity of the lung tissues and lower concentrations of the inflammatory cytokines in the BALF and lung tissues. Dexmedetomidine significantly inhibited the expression of [TLR.sub.4] and NF-[kappa]B and activation of NF-[kappa]B. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to H[V.sub.T]-MV and had a protective effect against VILI, with the inhibition of the [TLR.sub.4]/NF-[kappa]B signaling pathway, at least partly via [[alpha].sub.2]-adrenoceptors.
ISSN:1512-8601
DOI:10.17305/bjbms.2018.2400