The Protective Effect And Mechanism Of Dexmedetomidine On Acute Lung Injury Of Septic Mice

Objective: Mice sepsis induced acute lung injury model was established through the intraperitoneal injection of lipopolysaccharide (LPS), investigate the protective effect and potential mechanism of Dex and ?-Bgt on sepsis induced ALI in mice by estimating pathological changes of lung tissues, protein exudation, edema,inflammatory cell exudation, inflammation cytokine and oxidative stress levels and NF-?B signaling pathway protein expression.Methods: One hundred male BALB/c mice, weighing 18-20 g, aged 8-10 weeks,were randomly divided into five groups: control group, LPS group, Dex+LPS group,?-Bgt+Dex+LPS group, and ?-Bgt +LPS group. Lung tissues and plasma were harvested 2 hour after saline/LPS injection. The BALF and lung tissues were collected immediately. HE staining was used to observe the pathological changes of lung tissue. Inflammatory cells (the total number of cells, neutrophils, macrophages)were counted in BALF. Protein concentrations were determined by BCA method.Lung tissue wet to dry weight ratios were measured.The concentrations of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in lung tissues were measured,respectively, by ELISA. The expression of TNF-?, IL-6 and IL-lp mRNA in lung tissues were measured by RT-PCR. Western blotting was used to analyze the activation of NF-?B and I?B.Results: Compared with the control group, the histological pathology change of mice lung tissue were increased, the total number of inflammatory cell count in BALF were increased, the concentrations of TNF-a, IL-6 in lung tissues were increased, the expressions of TNF-?, IL-6 mRNA and the activation of NF-?B and I?B were significantly up-regulated in LPS group, the survival was decreased (P<0.05).Compared with the LPS group, the histological pathology change of mice lung tissue were decreased, the total number of inflammatory cell count in BALF were decreased,the concentrations of TNF-?, IL-6 in lung tissues were decreased, the concentrations of TNF-?, IL-6 in lung tissues were decreased, the expressions of TNF-?, IL-6 mRNA and the activation of NF-?B and I?B were significantly down-regulated in Dex+LPS group, the survival was up-regulated (P<0.05). Compared with the Dex+LPS group,the histological pathology change of mice lung tissue were increased, the total number of inflammatory cell count in BALF were increased, the concentrations of TNF-a,IL-6 in lung tissues were increased, the concentrations of TNF-?, IL-6 in lung tissues were increased, the expressions of TNF-?, IL-6 mRNA and the activation of NF-?B and I?B were significantly up-regulated in ?-Bgt+Dex+LPS group, the survival was decreased (P<0.05). There was no statistical difference in the parameters mentioned above between LPS group and ?-Bgt+LPS group.Conclusion: Dex attenuates acute lung injury of septic mice by activating the cholinergic anti-inflammatory pathway.