颅脑创伤（TBI）后继发性肺损伤是患者致死、致残的重要原因，且缺乏早期干预手段。本项目组首次报道了TBI后循环血中脑源性细胞外线粒体(exMT)增加，其可导致凝血功能紊乱，引起肺微血栓形成（Blood 2016; Haematologica 2019），并且exMT可介导血小板激活。有理由推测：TBI后exMT可能通过介导血小板激活和肺血管内皮损伤导致继发性肺损伤的发生发展。本项目拟进一步探索：1）TBI后血中exMT及微粒清除蛋白Del-1的动态变化及其与继发性肺损伤的关系；2）TBI后exMT通过CL/CD36信号轴介导血小板-内皮细胞激活级联反应及肺微血管屏障开放导致继发性肺损伤的分子机制；3）TBI后exMT的清除机制，探明微粒清除蛋白Del-1对exMT的清除及TBI后继发性肺损伤的影响。通过研究深入认识exMT在TBI后继发性肺损伤中的作用及机制，为其临床诊疗提供新思路。

Secondary lung injury after traumatic brain injury (TBI) is an important cause of mortality and mobility, and there is a lack of early intervention. For the first time, our team reported that exMT increased after TBI, leading to coagulation dysfunction and pulmonary microthrombosis (Blood 2016; Haematologica 2019), and exMT could activate platelets. Therefore, it is assumed that exMT release after TBI plays an important role in the occurrence and development of secondary lung injury after TBI mediated by platelets activation and injury of blood endothelial cells in the lung. This project intends to utilize transgenic mice, mouse TBI models, ion-conducting microscopy and other approaches to: 1) explore the dynamic changes of exMT and Del-1 in blood after TBI and their relationship with secondary lung injury; 2) explore the molecular mechanism of secondary lung injury induced by exMT after TBI through CL/CD36 signaling axis mediated platelet-endothelial cell activation cascade reaction and lung microvascular barrier opening; 3) investigate the effect of Del-1 on exMT clearance and secondary lung injury after TBI. By elucidating the early occurrence mechanism of secondary lung injury after TBI, we aim to provide new ideas for clinical diagnosis and treatment.