[Glabridin reduces lipopolysaccharide-induced lung injury in rats by inhibiting p38 mitogen activated protein kinase/extracellular regulated protein kinases signaling pathway].

To investigate whether glabridin has a beneficial effect on lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in rats, and to explore the possible underlying mechanisms. Thirty-two Wistar rats were randomly assigned into control group, model group (LPS group), glabridin group (GLA group), and ulinastatin group (UTI group), with 8 rats in each group. ARDS rat model was reproduced by intraperitoneal injection of LPS (10 mg/kg). The rats in the control group received an equal volume of normal saline at the same times. The rats in GLA group were gavaged by glabridin (30 mg/kg). The rats in UTI group were injected ulinastatin (20 000 U/kg). Animals were sacrificed 12 hours after LPS challenge. Plasma and lung tissue samples were collected. Histopathological evaluation, lung wet/dry (W/D)ratio, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase(SOD)were analyzed. Immunohistochemical method was used to detect the protein expression of p38MAPK and ERK. Western blot method was used to detect the changes of p38 mitogen activated protein kinase (p-p38MAPK) and phosphorylated extracellular regulated protein kinases (pERK) protein expression in lung tissues. In the control groups, lung tissue showed a normal structure and clear pulmonary alveoli under a light microscope. In the model group, ARDS characters such as extensive thickening of the alveolar wall, significant infiltration of inflammatory cells, demolished structure of pulmonary alveoli, and hemorrhage were found. In the GLA and UTI treatment group, these pathological changes in lung were markedly alleviated compare with LPS-induced ARDS group. Compared with control groups, lung W/D ratio, TNF-α and IL-18 in plasma, and lung MDA, NO levels in lung homogenates of the LPS group were increased significantly, while the lung SOD levels of the LPS group were decreased. Compared with the LPS group, lung W/D ratio, TNF-α and IL-18 in plasma , and lung MDA, NO levels in lung homogenates of the GLA group and UTI group were decreased significantly, while the lung SOD levels of the GLA and ulinastatin groups were increased [TNF-α(μg/L): 51.7±10.3 vs 105.7±30.5, IL-18(μg/L): 37.9±13.9 vs 49.2±14.5, MDA (nmol/mgprot): 2.87±0.62 vs 3.81±0.42, NO(μmol/L): 18.96±0.79 vs 28.58±2.51, SOD(U/mgprot): 115.5±15.2 vs 75.9±14.0, all <0.05]. Immunohistochemistry showed that the positive expressions of p38MAPK and ERK in cytoplasm and nucleus of the glabridin and ulinastatin treatment group were significantly lower than those of the model group. Western blot showed that compared with the control group, the p-p38MAPK and pERK protein expression in LPS group were significantly increased. And the glabridin and ulinastatin inhibited the protein expressions compared with model group. Traditional Chinese medicine glabridin significantly ameliorated the lung injury induced by LPS in rats via reducing inflammation which caused by the inhibition of p38MAPK and ERK signaling pathway and antioxidant effect.