Dexmedetomidine makes the anti-inflammation effect by blocking p38 mitogen-activated protein kinase in the lipopolysaccharides-induced acute lung injury in rats

Abstract

Objective The aim of this study was to determine whether dexmedetomidine (Dex) could diminish lipopolysaccharide(LPS)-induced pulmonary injury by blocking lung p38 mitogen-activated protein kinase(p38MAPK) activation and inflammation in rats.Methods A total of 50 adult male SD rats were assigned to one of five groups:0.9％ sodium chloride group (C group),LPS group (LPS group) and LPS plus Dex groups (0.2,1,5 μg/kg per hour) (Dex0.2 group,Dex1 group and Dex5 group).The rats in the LPS plus Dex groups were injected a loading dose of Dex (1 μg/kg per hour,intravenous infusion over 10 minutes) followed by LPS administration and Dex infusion at different doses (0.2,1,5 μg/kg per hour,respectively) until the end of experiment.Simultaneously,the LPS and control groups received an equal volume of 0.9％ sodium chloride(1 ml/kg per hour) till the end of experiment.Western blot was used to detect the expression of phosphorylation of p38MAPK in lung tissues.Additionally,we examined the concentration of tumour necrosis factor-α(TNF-α) and interleukin(IL)-10 in bronchoalveolar lavage fluid(BALF),the histopathologic changes of lung,arterial blood gases and lung water content.Results With the administration of LPS,arterial oxygen partial pressure was significantly decreased (61.3±1.2) vs (131.7±4.7) (P＜0.05),Pathological examination showed that the normal structure of lung was destroyed badly after LPS injection,including intra-alveolar hemorrhage,interstitial edema,alveolar collapse and massive inflammatory cells infiltration,The lung water content was significantly increased (5.4±0.3) vs (3.6±0.2)(P＜ 0.05).Compared with the LPS group,lung water content of Dex5 group was significantly decreased(4.4±0.4) vs (5.4±0.3)(P＜0.05).With the administration of LPS,the phospho-p38 MAPK substantially increased immediately,and the concentrations of cytokines were also increased.However,Dex at the dose of 5.0 μg/kg per hour,but not at 0.2 or 1.0 μg/kg per hour,significantly attenuated these effects of LPS (P＜0.05).Conclusions Dex may attenuate LPS-induced acute lung injury via inhibiting p38MAPK activation and lung inflammation. Key words: Dexmedetomidine; Anti-inflammatory effect; p38 mitogen-activated protein kinase; Lipopolysaccharides; Acute lung injury