Protective effect of liraglutide on acute lung injury in septic mice and its mechanism
Objective To explore the protective effects of liraglutide on acute lung injury in septic mice and its mechanisms.Methods Thirty-six male FVB/NJ mice were randomly(random number)divided into three groups:control group(Control,n=12),acute lung injury group(ALI,n=12)and liraglutide intervention group(ALI+LIRA,n=12).Mice model of acute lung injury were prepared by intratracheal instillation of Pseudomonas aeruginosa suspension,while the control group were given intratracheal instillation of equal volume of physiological saline;the mice in ALI+LIRA group were received subcutaneous injection of liraglutide(2 mg/kg)30 minutes post-induction,while both the mice in control group and ALI group were received subcutaneous injection of equal volume physiological saline.After 24 hours,the mice were euthanized,the lung tissues and bronchoalveolar lavage fluid(BALF)were collected,the lung pathological damage changes were evaluated by hematoxylin eosin staining,the expression of surfactant associated protein D(SP-D)in lung tissue were detected by immunofluorescence assay;total protein concentration in BALF were detected by BCA method,and the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)levels in BALF were measured by enzyme-linked immunosorbent assay(ELISA),the protein expression of SP-D in BALF and lung tissue were determined by Western blot.Statistical analysis was performed by SPSS software,and continuous variables were compared with one-way analysis of variance among the groups.Results Compared with the control group,the mice in ALI group had higher lung histopathology injury score,higher total protein concentration,higher IL-6 and TNF-α levels in BALF,and had less SP-D positive cells in lung tissue;and also had lower expression of SP-D in both BALF and lung tissue,with statistical significance(all P<0.05).Compared with ALI group,the mice in ALI+LIRA group had lower lung histopathology injury score,lower total protein concentration,lower IL-6 and TNF-α levels in BALF,and had more SP-D positive cells in lung tissue;and also had higher expression of SP-D in both BALF and lung tissue,with statistical significance(all P<0.05).Conclusions Liraglutide attenuates the severity of acute lung injury in septic mice,and its protective mechanism may be associated with the promotion of SP-D secretion.
LiraglutideSepsisPseudomonas aeruginosaAcute lung injuryMiceInflammatory cytokinesSurfactant associated protein DSecretion