Impact of geniposide on lung injury in rats with acute respiratory distress syndrome by regulating AMPK/SIRT1/NF-κB signaling pathway
Objective:To investigate the impact of geniposide(GE)on lung injury in rats with acute respiratory distress syn-drome(ARDS)by regulating AMP-activated protein kinase(AMPK)/silencing information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods:The ARDS rat model was established by tracheal instillation of lipopolysaccharide(LPS).Fifty rats after modeling were randomly group into ARDS group,GE low-dose(GE-L,12.5 mg/kg GE)group,GE medium-dose(GE-M,25 mg/kg GE)group,GE high-dose group(GE-H,50 mg/kg GE)group and GE-H+Compound C(AMPK inhibitor,50 mg/kg GE+250 µg/kg Compound C)group,another 10 normal rats were used as the control group.After the intervention,the bronchoalveolar la-vage fluid(BALF)and lung tissue of the rats in each group were taken out,respectively,and the ratio of lung wet to dry weight(W/D)was detected;ELISA was used to detect the levels of inflammatory factors IL-6,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)in BALF;the positive expressions of vascular cell adhesion factor(VCAM-1)and vascular endothelial cell growth factor(VEGF)in lung tissue were detected by immunohistochemistry;HE staining was used to observe the pathological changes of lung tissue;Western blot was used to detect the expression levels of AMPK/SIRT1/NF-κB pathway proteins in lung tissue.Results:The levels of W/D,IFN-γ,IL-6,TNF-α,p-NF-κB p65/NF-κB p65 and VCAM-1 in ARDS group were significantly higher than those in control group,the expressions of p-AMPK/AMPK,SIRT1 and VEGF were significantly decreased(P<0.05);after different doses of GE treatment,the levels of W/D,IFN-γ,IL-6,TNF-α,and the expressions of p-NF-κB p65/NF-κB p65 and VCAM-1 were gradually decreased compared with those in ARDS group;the expressions of p-AMPK/AMPK,SIRT1 and VEGF increased gradually(P<0.05);Compound C reversed the protective effect of GE-H on ARDS rats(P<0.05).Conclusion:GE can improve lung injury in ARDS rats and reduce levels of inflammatory factors,which may be related to activation of AMPK/SIRT1/NF-κB signaling pathway.
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