Preconditioning With Dexmedetomidine Has Protective Effects On Lipopolysaccharide-induced Lung Epithelial Cell Injury In Vitro.

BackgroundMultiple organ dysfunction syndrome（MODS）is the main cause of death in intensive care unit（ICU）because of its serious course,high mortality and high cost.Lung is usually the first organ impaired in the development of MODS in critically ill patients.It is manifested as acute lung injury/acute respiratory distress syndrome（ALI/ARDS）characterized by increased inflammation,hypercoagulability,low fibrinolysis and increased vascular and epithelial permeability.ALI/ARDS is closely related to the high mortality rate of MODS.Therefore,it is necessary to clarify the pathogenesis and drug treatment of ALI/ARDS.Dexmedetomidine（Dex）is a highly selective alpha 2 adrenergic receptor agonist.It was developed by Orion Pharma（Finland）and Abott（United States）Co.Ltd.as an imidazole derivative while officially approved for clinical use in China in 2009.It has proved from many clinical practice that Dexmedetomidine is not only used for sedation,analgesia,anti-anxiety,alleviation of alcohol withdrawal symptoms and reduction of sympathetic nerve tension,but also has good therapeutic effect and has achieved certain results in comfort and safety of perioperative.In recent years,the research of Dexmedetomidine on the protection of brain,heart,liver,lung and other important organs has become particularly topical.Many studies have shown that Dexmedetomidine has a protective effect on lung injury,however its mechanism is not very clear.ObjectiveThis study investigates the protection conferred by Preconditioningα₂ adrenoceptor agonist Dexmedetomidine from lung alveolar epithelial cell（A549）injury induced by LPS,and in order to provide theoretical basis for clinical treatment of acute lung injury（ALI）caused by multiple organ dysfunction syndrome.MethodsWe incubated A549 cells with LPS in the presence or absence of Dexmedetomidine.Dexmedetomidine was given before LPS stimulation in cells,alone or with atipamezole.It was divided into 4 groups:control group（Control）,Dexmedetomidine group（Dex）,Lipopolysaccharide treatment group（LPS）,Dexmedetomidine+LPS group（Dex+LPS）and atipamezole+Dexmedetomidine+LPS group（Ati+Dex+LPS）.MTT assay was used to detect the inhibition rate.Oxygen reactive species（ROS）was detected by DCFH-DA probe,mitochondrial membrane potential（MMP）was measured by JC-1 and Cell apoptosis was examined by Hoechst/PI staining.The expression of Bax,Bcl-2 was measured by western blot.ResultsUpregulation of ROS generation,MMP and apoptosis（P<0.05）were found on LPS-induced lung epithelial cell.All of these were reversed by Dexmedetomidine.Preconditioning with Dexmedetomidine also prevented the increases of cell apoptotic rate,Bax and Bcl-2 expression（P<0.05）induced by LPS.It also shows that atipamezole weaken the positive effects of Dexmedetomidine.ConclusionPreconditioning with Dexmedetomidine has protective effects on LPS-induced lung epithelial cell injury in vitro.It shows that Dexmedetomidine attenuates LPS-induced oxidative stress,protect mitochondrial function and inhibit the expression of apoptotic signals.Furthermore,the positive effects were partially inhibited by antagonist of?₂receptors atipamezole.