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Abstract
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BACKGROUND: Seawater drowning is the major cause of accidental injury and death. The current treatment could not essentially block the source of the damage due to the complex etiology. Therefore, it is urgent to clarify the detailed mechanisms and find effective therapeutic approaches.
METHODS: We performed in vitro experiments to evaluate the damage of seawater drowning to lung epithelial cells. FACS, immunofluorescent staining, and western blot were used to detect the apoptosis. CCK-8 assay, Ki67 staining, and cell cycle analysis were used to assess the proliferation. The cytokine expression was determined by qRT-PCR and ELISA. Western blot and reporter assay were used for regulation mechanism study. For neutrophils development, Transwell assay and FACS were used for further investigation. Besides, in vivo study was performed with the seawater drowning model in rats.
RESULTS: In this study, we found that seawater drowning induced mitochondria damage, which further accelerated epithelial cell apoptosis and repressed cell proliferation. Administration of ghrelin attenuated the mitochondria damage via reducing ROS generation, decreasing the concentration of calcium ion and ceremide, and promoting ATP production. Besides, exogenous ghrelin also rescued the cell survival inhibited by seawater simulants. Mechanically, ghrelin retrieved the influence of seawater via inhibiting NF-κB signaling activation, and agonist of NF-κB could offset the function of ghrelin. Besides, ghrelin reduced the expression of inflammatory factors and chemokines responsible for neutrophils activation and recruitment, by which ghrelin suppressed the immune response. The further in vivo experiments also indicated that ghrelin treatment restored the apoptosis promotion and inflammation activation function of seawater simulants, and further alleviated the lung tissue injury.
CONCLUSIONS: Our study revealed the dual effect of ghrelin on seawater drowning induced lung injury via damage protection and immune repression, providing new insights into drowning injury pathogenesis and therapeutic strategies.
Language: en |