动物造模,急性肺损伤 z-bio 2022-09-07 224

　　Objective To evaluate the mechanism of ceramides in aged platelets on transfusion-related acute lung injury.

　　Methods The TRALI double-hit model was established in BALB/c mice by pre-stimulation with lipopolysaccharide, followed by infusion of 10 mL/kg of platelets stored for 1-5 days. The acid sphingomyelinase specific inhibitor ARC39 or the infusion of platelets from acid sphingomyelinase-deficient mice were used to intervene in TRAIL model mice, and the sphingomyelin components in the platelets of mice at different time points and the sphingomyelin content in the lungs of TRAIL model mice were evaluated. The accumulation of neutrophils, endothelial barrier function, and the degree of lung histopathological damage.

　　RESULTS: Infusion of platelets stored for 1-5 days into lipopolysaccharides (LPS) pre-stimulated C57/B6 mice could induce characteristic damage of lung tissue, and the severity of the damage increased with the increase of platelet storage time. Ceramides in platelets are continuously accumulated and released during storage. Compared with the control group, platelets pretreated with ARC39 or platelets deficient in acid sphingomyelinase can significantly alleviate the damage of lung tissue.

　　Conclusion Aging platelets can lead to TRALI in mice, but this damage can be reversed and treated by acid sphingomyelinase inhibitors or specific knockout of the acid sphingomyelinase gene. Interventions targeting sphingolipid formation are expected to increase blood production Effective strategies for storage security and longevity.