Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway

  • Hongli Chen Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Xiaotong Sun Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Xiaomei Yang Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Yonghao Hou Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Xiaoqian Yu Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Yang Wang Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Jianbo Wu Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Dejie Liu Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Huanliang Wang Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Jingui Yu Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • Wenbo Yi Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Keywords: Dexmedetomidine, ventilator-induced lung injury, VILI, Toll-like receptor 4, TLR4, Nuclear factor κB, NF-κB, inflammatory cytokine, α2-adrenoceptor

Abstract

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 (HVT) MV (HMV), HVT MV + dexmedetomidine (DEX), HVT 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]-1β, tumor necrosis factor alpha [TNF-α], and IL-6) in the bronchoalveolar lavage fluid (BALF) and lung tissues, expression of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB, and activation of NF-κB 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 TLR4 and NF-κB and activation of NF-κB. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to HVT-MV and had a protective effect against VILI, with the inhibition of the TLR4/NF-κB signaling pathway, at least partly via α2-adrenoceptors.

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Author Biographies

Hongli Chen, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Xiaotong Sun, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Xiaomei Yang, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Yonghao Hou, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Xiaoqian Yu, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Yang Wang, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Jianbo Wu, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Dejie Liu, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Huanliang Wang, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Jingui Yu, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology
Wenbo Yi, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
Department of Anesthesiology

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Published
2018-05-20
How to Cite
1.
Chen H, Sun X, Yang X, Hou Y, Yu X, Wang Y, Wu J, Liu D, Wang H, Yu J, Yi W. Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway. Bosn J of Basic Med Sci [Internet]. 2018May20 [cited 2019Jun.16];18(2):162-9. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2400
Section
Pharmacology