OBJECTIVE: Acute lung injury (ALI) is the most common complication of sepsis, with rapid onset and high mortality. There is currently no effective treatment for ALI. Therefore, we looked for a good method of treating ALI by studying the effect and mechanism of Nesfatin-1 on ALI. MATERIALS AND METHODS: We used LPS to induce mouse and human alveolar epithelial cell line BEAS-2B to construct an ALI model. Recombinant Nesfatin-1 was administered subcutaneously to mice or used to stimulate BEAS-2B cells. We collected mouse bronchoalveolar lavage fluid and mouse lung tissue to detect changes in inflammatory factors and oxidative stress levels. In addition, we examined the expression changes of HMGB1 to study the mechanism of Nesfatin-1. RESULTS: Exogenous Nesfatin-1 significantly attenuated LPS-induced ALI and reduced inflammation levels and oxidative stress levels in mouse lung tissue. In cell experiments, Nesfatin-1 also reduced inflammation levels and oxidative stress levels in BEAS-2B cells. In addition, Nesfatin-1 reduced the expression of HMGB1 in mouse lung tissues and BEAS-2B cells, and decreased the activity of p38MAPK and NF-κB signaling pathways in the inflammation-related pathway downstream of HMGB1. However, after overexpression of HMGB1, the therapeutic effect of Nesfatin-1 on ALI was attenuated. CONCLUSIONS: Nesfatin-1 regulates the expression of HMGB1 in alveolar epithelial cells. By reducing the expression of HMGB1, Nesfatin-1 can reduce the inflammation-related signaling pathway downstream of HMGB1 to reduce the level of inflammation and oxidative stress in alveolar epithelial cells, thereby alleviating ALI.
OBJECTIVE: Acute lung injury (ALI) is the most common complication of sepsis, with rapid onset and high mortality. There is currently no effective treatment for ALI. Therefore, we looked for a good method of treating ALI by studying the effect and mechanism of Nesfatin-1 on ALI. MATERIALS AND METHODS: We used LPS to induce mouse and human alveolar epithelial cell line BEAS-2B to construct an ALI model. Recombinant Nesfatin-1 was administered subcutaneously to mice or used to stimulate BEAS-2B cells. We collected mouse bronchoalveolar lavage fluid and mouse lung tissue to detect changes in inflammatory factors and oxidative stress levels. In addition, we examined the expression changes of HMGB1 to study the mechanism of Nesfatin-1. RESULTS: Exogenous Nesfatin-1 significantly attenuated LPS-induced ALI and reduced inflammation levels and oxidative stress levels in mouse lung tissue. In cell experiments, Nesfatin-1 also reduced inflammation levels and oxidative stress levels in BEAS-2B cells. In addition, Nesfatin-1 reduced the expression of HMGB1 in mouse lung tissues and BEAS-2B cells, and decreased the activity of p38MAPK and NF-κB signaling pathways in the inflammation-related pathway downstream of HMGB1. However, after overexpression of HMGB1, the therapeutic effect of Nesfatin-1 on ALI was attenuated. CONCLUSIONS:Nesfatin-1 regulates the expression of HMGB1 in alveolar epithelial cells. By reducing the expression of HMGB1, Nesfatin-1 can reduce the inflammation-related signaling pathway downstream of HMGB1 to reduce the level of inflammation and oxidative stress in alveolar epithelial cells, thereby alleviating ALI.