Dexmedetomidine protects against sepsis-induced lung injury through autophagy and Smad2/3 signaling pathway
Author(s):
Zhanli Liu , Jiqing Xu , Yanqiu Zhao , Yanbin Wan , Rui Guo , Canling Long , Jia Liu , Xinhuang Yao * , Wenchao Yin
Article Type:
Research/Original Article (دارای رتبه معتبر)
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:
Acute lung injury , Autophagy , Dexmedetomidine , Sepsis , Smad2 , 3
Language:
English
Published:
Iranian Journal of Basic Medical Sciences, Volume:27 Issue: 4, Apr 2024
Pages:
453 to 460
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