Protective effects of dexmedetomidine on alveolar epithelial cells in sepsis mice
10.16781/j.0258-879x.2018.04.0388
- Author:
Fang XIE
1
Author Information
1. Intensive Care Unit, Department of Anesthesiology, Changhai Hospital, Navy Medical University, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Alveolar epithelium;
Dexmedetomidine;
Lipopolysaccharide;
Mouse;
Sepsis
- From:
Academic Journal of Second Military Medical University
2018;39(4):388-393
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of dexmedetomidine (DEX) in the inflammatory response of alveolar epithelial cells in sepsis mice. Methods Male C57BL/6 mice were randomly divided into cecal ligation and puncture (CLP) group and CLP＋DEX group (n＝36). The mice in the CLP group were intraperitoneally treated with 1 mL sterile normal saline and the mice in the CLP＋DEX group were intraperitoneally injected with DEX (50 μg/kg) at 15 min before CLP. The survival rate of mice was recorded within 24 h after CLP. The serum and bronchoalveolar lavage fluid (BALF) were collected on 0, 6, 12, 24 h after CLP, and the levels of interleukin (IL)-6, IL-1β and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The mouse alveolar epithelial cell lines MLE12 were cultured in vitro, and were divided into lipopolysaccharide (LPS) group (1 μg/mL LPS) and LPS＋DEX group (1 μg/mL LPS＋0.2 μg/mL DEX). The levels of IL-6, IL-1β and TNF-α in the cell supernatants were measured by ELISA, and the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) were determined by Western blotting on 6, 12 and 24 h of cell culture. Results Compared with the CLP group, the survival rate of mice was significantly higher in the CLP＋DEX group within 24 h after CLP (P0.05). The IL-6, IL-1β, and TNF-α levels of serum and BALF were significantly lower in the CLP＋DEX group than those in the CLP group (P0.05, P0.01). Compared with the LPS group, the levels of IL-6, IL-1β and TNF-α were significantly lower in the MLE12 cell supernatant of the LPS＋DEX group on 6, 12 and 24 h of cell culture (P0.05, P0.01). Western blotting results showed that the phosphorylation levels of ERK1/2 on 6, 12 and 24 h of cell culture and the phosphorylation levels of JNK on 6 and 12 h of cell culture were significantly lower in the LPS＋DEX group than those in the LPS group (P0.05, P0.01). Conclusion DEX can reduce the production of inflammatory cytokines in the serum and BALF of sepsis mice and increase the survival rate in sepsis mice, which may be related to the inhibition effect of DEX against activation of ERK1/2 and JNK signal pathways.
