ABSTRACT
Objective:To investigate the mechanism of dexmetomidine (DEX) in improving lung injury in septic mice.Methods:Male C57BL/6 mice were randomly assigned to the blank group (NC), sham operation group (sham), cecal ligation and puncture group (CLP), and Dex treatment group (CLP+DEX), 36 mice per group. Mice in the CLP group were intraperitoneally injected with 1 mL sterile saline 15 min before CLP, and mice in the CLP + DEX group were intraperitoneally injected with 50 μg/kg DEX 15 min before CLP. The survival rate was recorded within 24 h after CLP. The mice were sacrificed at 0, 3, 6, 12, and 24 h after CLP, and lung tissues were collected. The expression levels of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in the lung of mice were detected by qPCR. RAW264.7 cell were cultured in vitro, LPS (100 ng/mL) and DEX (1 μ mol/L) were used to establish a cell model for studying the mechanism of Dex, and the expression of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in RAW264.7 cell model were detected by qPCR. In addition, the effect of lncRNA-HOTAIR on sepsis was explored in vivo and in vitro by knockdown or overexpression of HOTAIR.Results:The survival rate of the CLP+DEX group was higher than that of the CLP group within 24 h after surgery, and the levels of IL-6, IL-1β, and TNF-α in the lungs were significantly lower than those in the CLP group at 6, 12, and 24 h after surgery ( P<0.05). In addition, the level of lncRNA HOTAIR showed that the expression level of lncRNA HOTAIR in the lungs of mice were decreased after Dex treatment, and were decreased 1.1 times ( P<0.05), 4.0 times ( P<0.01) and 3.8 times ( P<0.01) at 6, 12, and 24 h, respectively. Compared with the NC group, knockdown of HOTAIR significantly decreased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.05), and overexpression of HOTAIR significantly increased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.01). Conclusions:DEX can reduce the production of inflammatory factors in the lungs of septic mice and improve the survival rate of septic mice. The mechanism may be related to the inhibition of HOTAIR expression.