Dexmedetomidine protects against sepsis-induced lung injury through autophagy and Smad2/3 signaling pathway

Document Type : Original Article

Authors

1 Department of Anesthesiology, Shenzhen People’s Hospital and Shenzhen Anesthesiology Engineering Center, the Second Clinical Medical College of Jinan University, Shenzhen, China

2 Department of Cardiothoracic Surgery, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, China

3 Central Laboratory, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, China

4 Department of Anesthesiology, Sichuan Provincial Orthopedic Hospital, Chengdu, China

Abstract

Objective(s): Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice. 
Materials and Methods: Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured.
Results: CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis.
Conclusion: Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 27, Issue 4
April 2024
Pages 453-460

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