1. Academic Validation
  2. Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signaling pathway in rats

Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signaling pathway in rats

  • Int Immunopharmacol. 2019 Sep;74:105717. doi: 10.1016/j.intimp.2019.105717.
Huayun Zhang 1 Jichen Sha 1 Xiujing Feng 1 Xueyuan Hu 1 Yongping Chen 1 Bei Li 1 Honggang Fan 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China. Electronic address: fanhonggang2002@163.com.
Abstract

Acute lung injury (ALI) is a serious complication of sepsis and an important cause of death in intensive care. Studies have shown that DEX can inhibit inflammation. However, the anti-inflammatory effect and protective mechanism of DEX in lipopolysaccharide (LPS) induced ALI are still unclear. ALI model was established by intraperitoneal injection of LPS (10 mg/kg) in Sprague-Dawley (SD) male rats. Firstly, at 4, 6, 8, 12 and 24 h after LPS treatment, lung injury including pathologic histology, lung edema, and inflammation were detected. The optimal time point for lung injury was determined to be 12 h, at which time DEX was added to further test. Furthermore, STAT3 Inhibitor (NSC74859) and GSK-3β Inhibitor (SB216763) were added to verify the role of STAT3, GSK-3β and NF-κB in ameliorated ALI. Our results show that DEX pretreatment significantly decreased lung Wet-to-Dry weight (W/D) ratio and MPO activity and ameliorated LPS induced lung histopathological alterations. In addition, we confirmed that DEX can increased the phosphorylation of STAT3 and GSK-3β, and inhibit the phosphorylation of nuclear factor-κB (NF-κB) p65 in the inflammatory response induced by LPS. What's more, NSC74859 inhibited the phosphorylation of STAT3 and reversed the protect effect of DEX on LPS. SB216763 inhibited the phosphorylation of NF-κB and reversed the damage effect of LPS and plays the same anti-inflammatory effect as DEX. In summary, our data demonstrated that DEX can ameliorate ALI induced by LPS through GSK-3β/STAT3-NF-κB pathway.

Keywords

Acute lung injury; Dexmedetomidine; GSK-3β/STAT3-NF-κB; LPS.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15146
    98.64%, STAT3 Inhibitor