深静脉血栓形成（DVT）后，巨噬细胞（Mφ）在血栓中大量浸润介导其自然溶解。前期研究发现静脉血栓溶解程度与早期其内Mφ数量正相关，而溶解不良的血栓中Mφ自噬水平低，凋亡比例高。血小板反应蛋白(TSP)-1在Mφ中具有强大的抗凋亡作用，但前期研究发现静脉血栓内Mφ的TSP-1表达较正常静脉低，而体外过表达TSP-1的Mφ自噬水平显著升高，凋亡水平显著下降，且自噬相关AMPK/mTOR蛋白表达上调；沉默TSP-1则可逆转该过程。由此假设：TSP-1可通过AMPK/mTOR信号通路增强Mφ自噬，减少其凋亡，促进静脉血栓溶解。本项目拟将过表达TSP-1的Mφ体外于LPS炎症刺激下培养，检测其自噬及凋亡水平;体内移植入TSP-1基因敲除小鼠下腔静脉血栓模型检测血栓溶解效率。应用TSP-1受体阻断剂及自噬激动/抑制剂探明DVT后自噬相关AMPK/mTOR信号通路变化及分子机制，为DVT治疗提供新思路。

After deep vein thrombosis (DVT), macrophage (Mφ) infiltrates in venous thrombosis to mediate its natural lysis. Previous studies have found that the degree of venous thrombolysis was positively associated with the number of Mφ in the early stage, with a low level of Mφ autophagy and a high proportion of apoptosis in the dysplastic thrombus. Thrombospondin (TSP)-1 has strong anti-apoptosis abilities in Mφ, but previous studies have found that TSP-1 expression in Mφ is lower in venous thrombosis, whereas the level of autophagy was significantly increased in Mφ overexpressing TSP-1 in vitro, with the level of apoptosis significantly decreased, and the expression of autophagy-related AMPK/mTOR protein up-regulated, while silencing TSP-1 inhibited the process. It is hypothesized that overexpression of TSP-1 enhances Mφ autophagy through the AMPK/mTOR signaling pathway, reduces apoptosis, and promotes venous thrombolysis. In this project, Mφ overexpressing TSP-1 was cultured in vitro under the stimulation of LPS inflammation, and transplanted into the inferior vena cava thrombosis model of TSP-1 knockout mice to detect autophagy, apoptosis and thrombolytic efficiency. The use of TSP-1 receptor blockers and autophagy agonists/inhibitors were to detect changes and molecular mechanisms of autophagy-associated AMPK/mTOR signaling pathways, which will provide new ideas for the treatment of DVT.