供体肾周ad-SVF对心脏死亡来源移植肾缺血再灌注损伤的修复作用及机制

心脏死亡捐献（DCD）已成为我国肾移植供体的重要来源，但在等待捐献、获取、保存和移植等过程中发生的缺血再灌注损伤（IRI），却是影响移植肾功能恢复的重要因素。前期研究发现，脂肪基质血管成分（ad-SVF）富含MSC、EPC等干细胞，可有效参与肾脏IRI的修复，具可快速获得，无需体外培养等优点。且肾周ad-SVF还可特异性分泌促红细胞生成素（EPO）等，但供体肾周ad-SVF对心脏死亡来源移植肾IRI的影响目前并不清楚。我们推测：供体肾周ad-SVF可对心脏死亡来源移植肾IRI产生重要的修复作用。本项目拟建立大鼠心脏死亡来源肾移植模型，采用流式细胞分选、microPET-CT示踪及转染等技术，探讨供体肾周ad-SVF对心脏死亡来源移植肾IRI小管上皮及管周毛细血管内皮微环境的影响，阐明MSC、EPC及EPO在供体肾周ad-SVF修复移植肾中的作用机制，可为DCD移植肾IRI的防治提供新途径。

Donor after cardiac death (DCD) has contributed to the major organ source for renal transplant in China. However, during the wait for donation, recovery, storage and transplantation procedures, renal allograft suffers severe ischemia reperfusion injury (IRI), which could influence the graft function greatly. Our previous studies have confirmed that adipose stromal vascular fraction (ad-SVF) is a group of heterogeneous cells including mesenchymal stem cell (MSC) and endothelial progenitor cell (EPC), which is characterized with potent renoprotection, easy approach and no need of in vitro culture. Furthermore, the SVF derived from the perinephric adipose could express erythropoietin (EPO) specificly. However, the effects of donor perinephric adipose derived SVF on the repair of injured DCD renal allograft remain elusive. Here comes our speculation, donor perinephric adipose derived SVF might exert renoprotective functions against IRI of DCD reanl allografts. In the current project, after the establishment of rat DCD transplant model, the in vitro and in vivo experiments will be conducted with the methods such as flow cytometry for cell isolation, microPET-CT, and gene transfection, with the aim to observe the therapeutic effects of donor perinephric adipose derived SVF on the peritubular capillaries and renal tubular epithelia, and explore the potential underlying mechanisms of MSC, EPC, and EPO, which will provide new therapeutic methods for the prevention and treatment of IRI of DCD renal allograft.