Effect of Metformin on Lung Injury in Rats with Stroke-related Pneumonia Based on Leptin-mediated PI3K/AKT Pathway
Objective:To explore the effect of metformin on lung injury in rats with stroke-related pneumonia and its effect on leptin-mediated phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.Methods:A total of 85 male SD rats without specific pathogen(SPF)were randomly divided into sham operation group,model group,leptin group,leptin+ PI3K/AKT inhibitor group,metformin group,metformin+leptin group,metformin+PI3K/AKT activator group,with 12 rats in each group,and 1 rat failed to be modeled.Arterial partial oxygen pressure(PaO2)was measured and oxygenation index(OI)was calculated.The levels of serum leptin,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)in bronchoalveolar lavage fluid were determined in each group.The wet/dry mass of the right lung was calculated.The left lung tissue pathology was observed.PI3K/AKT pathway protein levels were determined in lung tissue.Results:Compared with sham operation group,the lung injury of model group aggravated,the levels of PaO2 and OI decreased(P<0.05),the levels of serum leptin,TNF-α,IL-1β,and CRP,the wet/dry mass of right lung,the p-PI3K/PI3K and p-AKT/AKT of lung tissue increased(P<0.05).Compared with model group,the lung injury of rats in leptin group were aggravated,the levels of PaO2 and OI decreased(P<0.05),the levels of serum leptin,TNF-α,IL-1β,and CRP,the wet mass/dry mass of right lung,the p-PI3K/PI3K and p-AKT/AKT in lung tissue of rats increased(P<0.05).Compared with leptin group,the lung injury of rats in leptin+PI3K/AKT inhibitor group and metformin+leptin group reduced,the levels of PaO2 and OI increased(P<0.05),the levels of serum leptin,TNF-α,IL-1β,and CRP,the wet/dry mass of right lung decreased,p-PI3K/PI3K and p-AKT/AKT decreased in lung tissue of rats(P<0.05).Compared with metformin group,metformin+ PI3K/AKT activator group increased lung injury,PaO2 and OI levels decreased(P<0.05),serum leptin,TNF-α,IL-1β and CRP levels,wet/dry mass of right lung,p-PI3K/PI3K and p-AKT/AKT increased in lung tissue of rats(P<0.05).Conclusion:Metformin has a protective effect on lung injury in rats with stroke-related pneumonia,which may be achieved by inhibiting leptin-mediated PI3K/AKT pathway.
stroke-related pneumonialung injuryleptinmetforminphosphatidylinositol 3-kinase/protein kinase B pathway
万方数据
维普
