Abstract

To investigate the effects and mechanisms of Dexmedetomidine on inflammatory factors and mitogenactivated protein kinase related signaling pathways in alveolar lavage fluid of mice with acute lung injury induced by lipopolysaccharide. 36 clean-grade male Kunming mice were randomly divided into blank control group (normal control group), lipopolysaccharide-induced acute lung injury model group, and lipopolysaccharide+dexmedetomidine group, with 12 mice in each group. The lipopolysaccharide group mice were intraperitoneally injected with 0.1 ml 5 mg kg-1 Lipopolysaccharide, lipopolysaccharide+Dexmedetomidine mice were injected with 25 μg kg-1. Dexmedetomidine intraperitoneally with 0.1 ml and 1 h later with 5 mg kg-1. Lipopolysaccharide injected with 0.1 ml intraperitoneally and the blank control group mice were intraperitoneally injected with normal saline of the same volume as the lipopolysaccharide group. All mice in each group were sacrificed after intraperitoneal injection for 6 h, and their lung tissues were separated by thoracotomy and their bronchoalveolar lavage fluid was recovered for subsequent detection. Analysis groups of mice lung tissue pathology, compare groups of mice lung tissue pathology score, lung wet weight/dry weight (W)/(D), mitogen-activated protein kinase pathways (p38 lightning, extracellular signal regulating kinase, c-jun amino terminal kinase) and bronchoalveolar lavage fluid protein expression level of tumor necrosis factor alpha beta, interleukin-1β, myeloperoxidase, protein concentration. In the blank control group, lung tissue structure was basically normal and alveolar structure was intact. lipopolysaccharide group mice had obvious lung tissue damage, and inflammatory cells appeared in the alveoli, with significantly increased exudation of red blood cells and proteins. Lipopolysaccharide+Dexmedetomidine group mice lung tissue damage significantly improved, inflammatory cell infiltration decreased, and red blood cell, protein exudation significantly decreased. Lung histopathological scores and bronchoalveolar lavage fluid levels of tumor necrosis factor alpha, interleukin- 1β and myeloperoxidase in lipopolysaccharide group were significantly higher than those in blank control group (p<0.05). The lung histopathological scores and the levels of tumor necrosis factor alpha, interleukin- 1β and myeloperoxidase in bronchoalveolar lavage fluid of lipopolysaccharide+Dexmedetomidine group were significantly lower than those of lipopolysaccharide group (p<0.05). The protein concentration in W/D and bronchoalveolar lavage fluid in lipopolysaccharide group was significantly higher than that in blank control group (p<0.05). Protein concentration in W/D and bronchoalveolar lavage fluid of lipopolysaccharide+Dexmedetomidine group was significantly lower than that of lipopolysaccharide group (p<0.05). The protein expression levels of extracellular signal regulating kinase, c-jun amino terminal kinase and P-P38 in THE lipopolysaccharide group were significantly higher than those in the blank control group (p<0.05). The protein expression levels of extracellular signal regulating kinase, c-jun amino terminal kinase and P-P38 in the lipopolysaccharide+Dexmedetomidine group were significantly lower than those in the lipopolysaccharide group (p<0.05). There was no significant difference in extracellular signal regulating kinase, c-jun amino terminal kinase and p38 protein expression levels in each group (p>0.05). Dexmedetomidine can significantly alleviate acute lung injury induced by lipopolysaccharide in mice, and its mechanism may be realized by blocking the activation of mitogen-activated protein kinaserelated signaling pathway and thereby reducing inflammatory response, providing a new target for the treatment of sepsis induced acute lung injury in the futurey.