Effects of dexmedetomidine on acute lung injury induced by lipopolysaccharide by regulating SIGIRR/NF-kB signaling / 中国药理学通报

ABSTRACT

Aim To explore the effect of dexmedetomidine (DEX) on acute lung injury (ALI) induced by lipopolysaccharide ( LPS) in rats and its mechanism. Methods The experiment included normal control group (Control) , DEX control group (DEX) , LPS-in-duced acute lung injury group (LPS) and LPS + DEX treatment group ( LPS + DEX ). Twenty-four hours after the successful modelling, the wet/dry weight ratio ( W/D) of the lung tissues of each group and the content of inflammatory cytokines IL-1 (3, TNF-a and IL-6 in the bronchoalveolar lavage fluid ( BALF) were measured; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissues; im- munohistochemistry and Western blot were used to detect the expression of SIGIRR and NF-kB in lung tissues. Results Compared with control group, the levels of IL-1 (3, IL-6 and TNF-a in lung tissues of LPS group and BALF increased (P <0. 01). The lung tis sues showed obvious pathological damage of ALI, and the expression of SIGIRR was reduced ( P < 0. 01), the expression of phosphorylation activation of NF-kB increased (P <0. 01). Compared with LPS group, the W/D of lung tissues in LPS + DEX group and IL-1 [}, IL- in BALF 6 and TNF-a content were reduced (P < 0. 05 or P < 0. 01 ) . The pathological damage of lung tissues was significantly reduced, SIGIRR expression increased, and the activation of NF-kB phosphorylation decreased (P < 0. 01 ). Conclusions Dexmedetomidine can reduce SIGIRR degradation, inhibit the activation of NF-kB and reduce the inflammation, thereby reducing the acute lung injury induced by lipopolysaccharide in rats.