Vaspin Protects Against LPS-induced ARDS By Inhibiting Inflammation And Protecting The Vascular Endothelium Via PI3K/Akt Signal

ObjectiveTo investigate the effects of Vaspin on LPS-induced acute respiratory distress syndrome(ARDS)in mice and to explore the possible mechanism.Methods1.Forty male C57BL/6J mice were randomly divided into 4 groups:control group,LPS group,Vaspin group(LPS+Vaspin),wortmannin group(LPS+Vaspin+wortmannin),with 10 mice in each group.2.ARDS was induced in C57BL/6J male mice by intratracheal administered of LPS.Twenty-four hours later,the mice were exsanguinated.3.The pathological changes of the lung tissues were observed by HE staining,The degree of pulmonary edema was measured by wet/dry ratio(W/D).The lung permeability was evaluated by the concentrations of total protein in bronchoalveolar lavage fluid(BALF)using bicinchoninic acid(BCA)assay.The lung myeloperoxidase(MPO)activity was detected by a MPO assay kit.The levels of tumeor necrosis factor-?(TNF-?)and interleukin(IL-1?)in lung tissue were measured by ELISA.The expression of vascular cell adhesion molecule-1(VCAM-1)in lung tissue was observed by immunohostochemical assay.While the expression levels of cleaved caspase-3 and p-Akt were determined by western blot.Results1.24 hours after LPS injection,compared with the control group,the typical ARDS pathological changes were observed in LPS group,and the wet/dry ratio(W/D),concentrations of total protein in bronchoalveolar lavage fluid(BALF)were significantly increased in LPS group(P<0.05),The deteriorating effects above triggered by LPS were significantly alleviated by the administration of Vaspin with a contrary observation in the indexes above(P<0.05),Furthermore,the effects of Vaspin on ARDS were reversed by the PI3 K inhibitor wortmannin(P<0.05).2.24 hours after LPS injection,compared with the control group,lung myeloperoxidase(MPO)activity,levels of tumeor necrosis factor-?(TNF-?)and interleukin(IL-1?)and the expression of vascular cell adhesion molecule-1(VCAM-1)in lung tissue were significantly increased in LPS group(P<0.05),The deteriorating effects above triggered by LPS were significantly alleviated by the administration of Vaspin with a contrary observation in the indexes above(P<0.05),Furthermore,the effects of Vaspin on ARDS were reversed by the PI3 K inhibitor wortmannin(P<0.05).3.24 hours after LPS injection,compared with the control group,the expression of cleaved caspase-3 were significantly were significantly increased in LPS group(P<0.05),The deteriorating effects above triggered by LPS were significantly alleviated by the administration of Vaspin with a contrary observation in the indexes above(P<0.05),Furthermore,the effects of Vaspin on ARDS were reversed by the PI3 K inhibitor wortmannin(P<0.05).4.24 hours after LPS injection,The levels of Akt phosphorylation were significantly decreased in LPS group compared with the control group(P<0.05),The deteriorating effects above triggered by LPS weresignificantly alleviated by the administration of Vaspin with a contrary observation in the indexes above(P<0.05),Furthermore,the effects of Vaspin on ARDS were reversed by the PI3 K inhibitor wortmannin(P<0.05).ConclusionVaspin protects against LPS-induced ARDS in the mice by inhibiting inflammation and protecting the vascular endothelium,at least partially,via activation of the PI3K/Akt signal pathway.