Clonidine inhibits inflammatory response in lung injury mice through cholinergic anti-inflammatory pathway

AIM:To explore the influence of clonidine on inflammatory response in lung injury mice and its possible mechanism.METHODS:Clonidine solution was intravenously injected into the mice with lung injury induced by LPS.The left upper lobe of the lung was collected to detect lung wet/dry weight ratio (W/D) and total lung water content (TLW).The concentrations of IL-6,IL-1β and TNF-α were measured by ELISA.The expression of α7 nicotinic acetylcholine receptor (α7nAChR) and high-mobility group box protein 1(HMGB1) at mRNA and protein levels was determined by RT-PCR and Western blot.After importing α7nAChR siRNA lentiviral vector or injecting exogenous HMGB1 protein,the inflammatory cytokines were detected.RESULTS:Clonidine attenuated lung injury and inhibited inflammatory reaction.Clonidine promoted the activation of cholinergic anti-inflammatory pathway by promoting α7nAChR expression.Clonidine inhibited HMGB1 expression,which promoted the secretion of IL-6,IL-1β and TNF-α.HMGB1 was negatively regulated by α7nAChR.CONCLUSION:Clonidine functions as an anti-inflammatory reagent to the lung injury mice.The mechanism may be related to activating the cholinergic anti-inflammatory pathway and inhibiting the expression of HMGB1.