Abstract: Objective: To establish the acute lung injury (ALI) mouse models induced by lipopolysaccharide (LPS),and to investigate the protective effect of berberine on ALI and its mechanism in vivo.Methods: A total of 40 C57BL/6 mice were randomly divided into control group, LPS group, berberine +LPS group and berberine group(n=10). The mice in control group were treated with saline;the mice in LPS group were treated with 5 mg·kg^-1 LPS for 6 h; the mice in berberine +LPS group were pretreated with 50 mg·kg^-1 berberine for 5 d before LPS treatment, then treated by 5 mg·kg^-1 LPS for 6 h;the mice in berberine group were pretreated with 50 mg·kg^-1 berberine for 5 d.The morphology of lung tissue of the mice in various groups were detected by HE staining. The ratios of wet to dry weights of lung tissue of the mice in various groups were detected. The concentrations of total protein and the number of effusion cells in bronchoalveolar lavage fluid(BALF) of the mice in various groups were detected; the levels of tumor necrosis factor(TNF-α) and interleukin-6(IL-6) in BALF of the mice in various groups were detected by ELISA method; the reactive oxygen species (ROS) levels in lung tissue of the mice in various groups were detected by dihydreethidium(DHE) method. The mitochondrial membrane potential in lung tissue of the mice in various groups were detected by JC-1 method.The expression levels of Bcl-2 and Bax proteins in lung tissue of the mice in various groups were detected by Western blotting method,and the ratios of Bcl-2/Bax were caculated.Results: Compared with control group, the inflammatory cell infiltration of lung interstitium and the alveolar space of the mice in LPS group were significantly increased, and the alveolar wall was thickened, the ratio of wet to dry weight of lung tissue was significantly increased (P<0.01), the level of total protein (P<0.05) and the number of exudation cells in BALF were increased (P<0.01),the levels of TNF-α and IL-6 in BALF were significantly increased (P<0.01), the ROS level in lung tissue was increased, the mitochondrial membrane potential in lung tissue was decreased (P<0.01),and the ratio of Bax/Bcl-2 in lung tissue was increased (P<0.01). Compared with LPS group, the inflammatory changes of lung tissue of the mice in berberine+LPS group were improved, the ratio of wet to dry weight of lung tissue was decreased (P<0.05), the level of total protein and the number of exudation cells in BALF were increased (P<0.05),the levels of TNF-α and IL-6 in BALF were decreased (P<0.01), the ROS level in lung tissue was decreased, the mitochondrial membrane potential in lung tissue was increased (P<0.05),and the ratio of Bax/Bcl-2 in lung tissue was decreased (P<0.05).Conclusion: Berberine could improve the degrees of LPS-induced ALI and inflammation of the mice,and the mechanism might be related to reduction of the ROS level and protection of mitochondrial function in lung tissue.

Key words: lipopolysaccharide, mice, acute lung injury, reactive oxygen species, mitochondria, berberine