M1巨噬细胞外泌体miR-126-5p通过可变剪接因子SRSF11调控内皮衰老及深静脉血栓发生的作用机制研究

深静脉血栓（DVT）是骨科大手术后发生率较高的并发症，也是患者围手术期死亡的重要因素之一，但目前DVT发生发展的病因和病理机制并不完全清楚。我们前期研究发现：DVT形成过程与M1巨噬细胞募集和内皮细胞衰老密切相关，且M1巨噬细胞可能通过外泌体与内皮细胞发生交互作用，促进DVT的形成，但是具体机制不清楚。进一步研究发现：M1巨噬细胞外泌体miR-126-5p表达上调，且与可变剪接因子SRSF11具有较好的靶向关系。结合前期实验数据，我们推测：在DVT发生发展过程中，M1巨噬细胞可能通过外泌体miR-126-5p—SRSF11—LncRNA Sirt1-AS—Sirt1信号轴调控内皮细胞的衰老。课题力图从细胞与细胞之间的交互作用切人，体内体外实验系统的揭示M1巨噬细胞调控内皮细胞衰老的分子调控网络，为更好的认识DVT病理机制提供理论依据，同时为临床治疗深静脉血栓疾病提供新靶点和新策略。

Deep vein thrombosis (DVT) is a complication with high incidence after orthopedic surgery, and it is also one of the important factors of perioperative death. However, the etiology and pathological mechanism of DVT are not completely clear at present. Our previous study found that the formation of DVT is closely related to M1 macrophage recruitment and endothelial cell aging, and M1 macrophages may interact with endothelial cells through exosomes to promote the formation of DVT, but the specific mechanism is not clear. Further study showed that the expression of mir-126-5p in exosomes of M1 macrophages was up-regulated and had a good targeting relationship with variable splicing factor srsf11. Combined with the previous experimental data, we speculated that M1 macrophages might regulate the senescence of endothelial cells through the signal axis of mir-126-5p-srsf11-lncrna sirt1-as-sirt1 during the development of DVT. The purpose of this study is to explore the molecular regulatory network of M1 macrophages regulating endothelial cell senescence in vitro and in vivo, and to provide a theoretical basis for better understanding of the pathological mechanism of DVT, as well as a new target and strategy for clinical treatment of DVT.