Experimental study of liraglutide on pulmonary inflammation in mice with acute lung injury
Objective To explore the effects of liraglutide on pulmonary inflammation in mice with acute lung injury(ALI)and its possible underlying mechanism.Methods A total of 72 mice were randomly divided into six groups:the control(Control)group,ALI group,dexamethasone(DXM)group,three liraglutide groups with low(LRLT_L),medium(LRLT_M)or high(LRLT_H)concentration.The ALI models of mice were established by the intraperitoneal(i.p.)injection of lipopolysaccharide(LPS)(15 mg/kg in PBS).The Control group was delivered with PBS only instead of LPS.The DXM group was injected with DXM(5 mg/kg in PBS).The LRLT_L,LRLT_M,and LRLT_H groups were respectively treated with low(10 μg/kg),medium(100 μg/kg)and high(800 μg/kg)dose of liraglutide intraperitoneally based on the ALI model.The levels of interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid were determined by ELISA.The level of nuclear factor-κB(NF-κB)p65 in lung tissue was measured by Western blotting.Results The TNF-α levels were different among the six groups(F=13.37,P＜0.05);the TNF-α in the ALI group increased in comparison with that in the Control group,LRLT_L group,LRLT_M group,LRLT_H group and DXM group,all the differences were statistically significant(t=7.46,5.61,4.44,6.38,3.35;all P＜0.01).The IL-10 levels were different among the six groups(F=66.85,P＜0.05).The IL-10 in the ALI group increased compared with that in the Control group(t=7.64,P＜0.01).The IL-10 levels in DXM group,LRLT_L group,LRLT_M group,LRLT_H group were significantly higher than that in the ALI group;all the differences were statistically significant(t=2.96,4.69,7.99,5.80;all P＜0.01).The NF-κB levels were different among the six groups(F=47.58,P＜0.05).Compared with the Control group,the NF-κB levels in the ALI group was significantly higher(t=10.80,P＜0.01).The NF-κB levels,in the LRLT_L group,LRLT_M group,and LRLT_H group were gradually decreased as the dose increased of liraglutide compared with that in the ALI group;all the differences were statistically significant(t=4.54,6.93,12.34;all P＜0.01).Compared with the DXM group,the NF-κB in the LRLT_L group or LRLT_M group were up-regulated;all the differences were statistically significant(t=7.40,5.01;all P＜0.05).Whereas that in the LRLT_H group showed no significant difference.Conclusion The liraglutide could inhibit the proinflammatory factor TNF-α but promote anti-inflammatory factor IL-10 expression and secretion in the ALI mice lung,which might be mediated by the downregulation of NF-κB signaling pathway.
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