脾破裂合并肢体骨折是临床常见的高能量多发伤，全脾切除是其首要急救措施。我们前期的研究表明脾切除可致骨折愈合延迟，但机制不明。我们在预实验中通过建立脾切除的大鼠股骨骨折模型，发现损伤部位巨噬细胞氨基酸转运蛋白CD98与xCT以及谷氨酰胺代谢中间产物α-酮戊二酸（α-KG）的水平显著降低，并伴随M1型巨噬细胞的减少及其表面α-KG受体GPR99表达的下调；此外发现，去泛素化酶UCHL1在间充质干细胞的骨向分化中发挥重要作用并受α-KG调控。据此提出，脾切除后巨噬细胞低表达CD98抑制了谷氨酰胺代谢及α-KG的分泌，从而一方面影响了自身表面GPR99与α-KG的配接，抑制M1型极化的转变，另一方面通过直接作用于MSCs中UCHL1的表达进而抑制骨向分化，最终延迟骨折愈合。该项目将进一步围绕脾切除后巨噬细胞代谢改变致骨折愈合延迟的作用机制进行深入研究，为发现重要的免疫调控靶点提供理论依据。

Bone fracture combined with splenic rupture is a common clinical symptom, and total splenectomy is the primary therapeutic method. Our previous study showed that splenectomy could delay fracture healing, but the mechanism remains unclear. In our preliminary study, the rat fracture model with splenectomy was established. We found that the levels of macrophage amino acid transporter CD98 and xCT, and glutamine metabolic intermediates α-ketoglutarate (α-KG) were downregulated, accompanied by decreased number of M1 macrophages and downregulated expression of surface α-KG receptor GPR99. Besides, the effect of ubiquitin C-terminal hydrolaseUCHL1 in mesenchymal stem cells (MSCs) on osteogenic differentiation was essential and is can be regulated byα-KG. Accordingly, we presume that the low expression of CD98 in macrophages after splenectomy inhibited glutamine metabolism and the secretion of α-KG, which in one aspect,directly affect the interaction of GPR99 and α-KG andthe polarization of M1 macrophage, on the other hand inhibit osteogenic differentiation via UCHL1 in MSCs, leading to delayed fracture healing. This project will further study the mechanism of macrophage-mediated delayed fracture healing, and provide theoretical evidence and clinical reference for finding important immunoregulatory targets.