小鼠模型中神经酰胺对血小板介导的输血相关急性肺损伤的作用  

Effect of ceramide on platelet-mediated transfusion-related acute lung injury in mice

作　　者：李应明[1] 陈华[1] 伍燕[1] LI Yingming;CHEN Hua;WU Yan(Department of Blood Transfusion,Haikou People’s Hospital,Haikou 570208,China)

机构地区：[1]海南省海口市人民医院输血科,海口570208

出　　处：《中国比较医学杂志》2020年第8期86-91,共6页Chinese Journal of Comparative Medicine

摘　　要：目的评价老化的血小板中的神经酰胺对输血相关急性肺损伤(transfusion-related acute lung injury,TRALI)的作用机制。方法通过脂多糖预刺激,随后输注10 m L/kg储存1~5 d的血小板,在BALB/c小鼠体内构建TRALI的二次打击模型。采用酸性鞘磷脂酶特异性抑制剂ARC39或输注来自酸性鞘磷脂酶缺乏小鼠的血小板对TRAIL模型小鼠进行干预,评价不同时间点小鼠血小板中鞘磷脂成分,以及TRAIL模型小鼠肺中性粒细胞积聚情况,内皮屏障功能,肺组织病理学损伤程度。结果存储1~5 d的血小板输注到脂多糖(lipopolysaccharides,LPS)预刺激后的C57/B6小鼠体内能够引起肺组织的特征性损伤,且损伤严重程度随血小板储存时间的增加而加剧。血小板中的神经酰胺在储存过程中不断积累和释放。与对照组相比,输注ARC39预处理后的血小板或酸性鞘磷脂酶缺乏的血小板可明显缓解肺组织的损伤。结论老化的血小板会导致小鼠发生TRALI,但这种损伤可以通过酸性鞘磷脂酶抑制剂或特异性敲除酸性鞘磷脂酶基因来逆转和治疗,针对鞘脂形成的干预措施有望成为增加血制品存储安全性和寿命的有效策略。Objective To evaluate the mechanism of ceramide in aged platelets mediated by transfusion-related acute lung injury(TRALI).Methods The second hit model of TRALI was established in mice via lipopolysaccharide prestimulation,and platelets were transfused and stored for 1-5 days.ARC39(a specific acid sphingomyelinase inhibitor)or platelets from acid sphingomyelinase-deficient mice were used to treat BALB/c mice.Temporal changes in platelet sphingomyelin composition were analyzed.We examined the accumulation of neutrophils in the lungs of TRALI mice,as well as the function of the endothelial barrier and the histology of injured lung tissue.Results Platelets were collected and stored for 1~5 days from mice prestimulated by LPS,which caused characteristic lung injury,and the severity of lung injury increased with time.Ceramide in platelets accumulated and decreased during storage.Compared with the control group,transfusion of ARC39 preconditioned platelets or acid sphingomyelinase deficient platelets significantly alleviated lung injury.Conclusions Aging platelets can lead to TRALI in mice,but this damage can be reversed and treated by an acid sphingomyelinase inhibitor or specific knockout of the acid sphingomyelinase gene.Such intervention measures for sphingolipid formation are expected to be an effective strategy for increasing the storage safety and shelf life of blood products.

关 键 词：输血相关性急性肺损伤 神经酰胺 酸性鞘磷脂酶 血小板 

分 类 号：R-33[医药卫生]