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

Authors

  • 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

DOI:

https://doi.org/10.17305/bjbms.2018.2400

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.

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

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Published

20-05-2018

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1.
Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway. Biomol Biomed [Internet]. 2018 May 20 [cited 2024 Mar. 29];18(2):162-9. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2400