由烧创伤、肿瘤等引起的截肢患者数量庞大，患者期望恢复肢体功能的愿望十分强烈，假肢能替代少部分功能，但存在可控性差、外形不美观、携带不便等诸多缺点。异体肢体移植目前是解决肢体残缺的有效手段，但是移植后的免疫排斥问题使得该技术难以临床推广，如何让肢体移植患者少用甚至不用免疫抑制剂是亟待解决的问题。我们在前期研究中发现雷公藤甲素(PG490)与他克莫司(FK506)联合使用能够的显著降低肢体移植术后期的免疫排斥反应，提高受体外周血嵌合水平，且在移植物以及宿主体内肥大细胞（mast cell, MC）比例显著升高。这一现象提示药物的联合应用可能促进肥大细胞增殖并参与降低免疫排斥反应。鉴于肥大细胞具有较强的分泌外泌体的功能，本次研究拟通过对联合用药诱导的MC分泌的外泌体内容物及其对其它免疫细胞的调节功能展开探索，以期获得MC调控免疫排斥的机理及靶点，为新型的免疫抑制剂的研发奠定基础。

A large number of amputed patients, caused by burn, trauma or tumor, expected to restore limb function. The prosthetic can only substitute a small number of functions, furthermore, there are other shortcomings such as uncontrollable, poor appearance carrying inconvenience. Limb allotransplantation is an effective method to solve the these problems, but immune rejection post transplantation makes it hard for the wide clinical application. Reducing the dosage of tranditional immunoxuppressants to minize drug-associated toxicities and induce donor-specific tolerance are two current hotspot in vascularized composite allotransplantation research. Our previous study has demonstrated that PG490, combined with FK506, can significantly decrease immune rejection and increase the level of peripheral blood chimerism of recipients. Also, the graft and the host of the mast cells (mast cell, MC) rates also increased significantly. This phenomenon might suggest that the combination of drugs may promote the proliferation of mast cells and participate in the reduction of immune rejection. Given the secretion of exsome of mast cells, we will explore the immnunological modulation of exsome secreted by MC, which is induced by combined immunosuppressants post allotransplatation, expecting to reveal the MC regulation mechanism of immune rejection and targets, so as to lay a foundation for the research and development of new immunosuppressant.