Dexmedetomidine protects against sepsis-induced lung injury through autophagy and Smad۲/۳ signaling pathway

Objective(s): Dexmedetomidine (Dex) is a potent α۲-adrenergic receptor(α۲-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 smad۲/۳ signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and smad۲/۳ is not clear. This study aimed to investigate the role of autophagy and the smad۲/۳ signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C۵۷BL/۶J mice. Materials and Methods: Mice were randomly assigned to four groups (n=۶ per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α۲-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an ۱۸-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, smad۲/۳ 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 smad۲/۳ 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 smad۲/۳ signaling pathway.

کلیدواژه ها:

Acute lung injury ، Autophagy ، Dexmedetomidine ، Sepsis ، Smad۲/۳