中性粒细胞胞外诱捕网（NETs）参与的炎症调控在游离脂肪移植后脂肪再生中的作用机制研究

Autologous fat should be considered as the most ideal soft tissue filler; however，it suffered from high absorption rate. Thus, a thorough understanding on the survival and regeneration mechanism of fat grafting is required. Our previous studies have found that adipose tissue regeneration is the key process after free fat transplantation. Moreover, the inflammation mediated by macrophages and neutrophil played an important role in the regulation of the fat tissue regeneration in fat grafting. By observing the tissue slice of the transferred fat, we accidentally found a structure closely related to the early inflammation, which was identified as neutrophil extracellular trap (NETs). This study intends to investigate the role of NETs on mature adipocytes and adipose stem cells, to characterize the relation between NETs and the inflammation activity in the fat grafts and to observe the influence of NETs on fat graft retention rate by depletion of the NETs in the fat grafts, expounding the close relationship between the NETs and fat graft survival / regeneration. This study will further reveal the inflammatory regulation mode after free fat transplantation, and provide a theoretical basis for guiding improving the fat graft retention rate by adjusting the level of NETs after fat transplantation.

游离脂肪是最理想的软组织填充剂，但其高吸收率是限制了其广泛临床应用。究其原因，关键在于缺乏对其存活及再生机制的深入了解。课题组前期研究发现，脂肪再生是游离脂肪移植后体积保留的核心机制，并且巨噬细胞和中性粒细胞介导的炎症反应是脂肪再生过程中最重要的调节因素。在移植脂肪的早期,我们在组织切片中发现了一种与炎症调控密切相关的结构,经鉴定为中性粒细胞胞外诱捕网（NETs）。本研究拟围绕NETs对成熟脂肪细胞及脂肪干细胞的活性、增殖与分化的影响、观察游离移植后脂肪组织内NETs与移植物炎症水平的关系及通过下调移植物中的NETs，观察其对游离脂肪移植保留率的影响这三部分内容，阐明NETs与脂肪存活/再生的密切相关性。本研究将进一步揭示游离脂肪移植后的脂肪再生的炎症调控模式, 并为通过调节脂肪移植后中的NETs水平来诱导游离脂肪移植物的再生提供理论依据。

自体脂肪移植技术是整形外科领域治疗组织缺损和修复局部凹陷最常用的技术手段。目前对于移植后脂肪的转归不明，脂肪移植后结节的发生原因不清，对其处理原则又没有统一的标准，这些都极大的限制了脂肪移植在临床上的应用。本项目组围绕游离脂肪移植的存活机制及其移植后的组织演变转归进行了一系列研究，确定了炎症细胞在脂肪移植过程中的重要作用；且项目组在研究中首次发现，宿主筋膜来源巨噬细胞介导的炎症调控在游离脂肪移植纤维化过程中起到重要作用。本研究基于上述发现，重点关注移植物中的炎症反应和脂肪新生及纤维化之间的调控关系，为良性引导脂肪移植物转归提供理论基础和实验依据。