Glabridin Alleviates Lipopolysaccharide Induced Lung Injury By Regulating MLK3-MKK3/6-P38MAPK Axis

Object: In order to provide practical basis for clinical treatment of septic lung injury,the mechanism of this signaling pathway in septic lung injury was studied and analyzed by using lipopolysaccharide(LPS)-induced rat model of septic lung injury.Methods: Wistar rats were randomly divided into 5 groups(8 in each group): Control(Ctrl)sepsis group(LPS)+Glabridin(LPS+Glabridin)sepsis +MLK3 inhibitor K252 a group(LPS+K252a)The changes of interleukin 18(IL-18),tumor necrosis factorα(TNF-α),macrophage inflammatory protein 2(MIP-2)in lung tissues of rats in sepsis+P38MAPK inhibitor SB203580 group(LPS+SB203580)were determined by Elisa.HE staining of lung tissue was observed under light microscope.The changes of p-P38 MAPK,p MLK3,PMKK3/6 were determined by Western-Blot.Results: 1.Pathological results of HE staining of lung tissue showed that inflammatory cells infiltrating alveolar edema accumulated in the glabridinin group and the inhibitor group was significantly reduced in the sepsis group.2.The results of il-18 TNF-α MIP-2 in lung tissue showed that the inflammatory factors produced by the sepsis group were significantly increased,and the glabridin group and the inhibitor group could effectively reduce the production of inflammatory factors.The difference of IL-18 between LPS group and other groups was significant(F=8.02,P<0.05);TNF-α in LPS group was significantly different from other groups(F=18.68,P<0.05);There was significant difference between LPS group and other groups in MIP-2(F=15.42,P<0.05);3.Western-blot(WB)results showed that LPS group of P-MLK,P-MKK3/6 and P-P38 MAPK were significantly different from other groups,P<0.05 These results suggest that lipopolysaccharide can significantly increase the number of neutrophils/macrophages and the level of inflammatory molecules(tumor necrosis factor-α MIP-2 IL-18)in bronchoalveolar lavage fluid in rats.Conclusions: Glabridin ameliorates the production of recruiting cytokines and chemokines by inflammatory cells(neutrophils and macrophages)and pulmonary edema These results suggest that glabridin may inhibit lung inflammation in ARDS rats by inhibiting the recruitment of inflammatory cells and the secretion of inflammatory molecules,thus playing a protective role.Visible light glabridin can reduce septic lung injury by regulating ml K3-MKK3/6-P38 MAPK axis.