供体凋亡脾细胞输注诱导大鼠胰岛移植免疫耐受的研究

目的 探讨供体凋亡细胞输注诱导大鼠胰岛移植免疫耐受的可行性.方法 应用链脲佐菌素(STZ)制备SD大鼠糖尿病模型,以直线加速器照射诱导供体Wistar大鼠脾细胞凋亡.将糖尿病SD大鼠分为4组,分别经阴茎背静脉输注Hanks液、供体正常脾细胞、供体凋亡脾细胞、供体坏死脾细胞,7天后于肾包囊进行同种异体胰岛移植,测定血糖变化,观测胰岛移植物存活时间,并通过混合淋巴细胞反应(MLR)观察移植耐受的状态.结果 预输注供体凋亡脾细胞能显著延长同种异体胰岛移植物存活时间(中位存活时间达31天),并使受体鼠对供体鼠的MLR明显减弱.结论 供体凋亡细胞输注能够诱导同种异体大鼠胰岛移植免疫耐受.

Immunological tolerance of rat pancreatic islet transplantation induced by transfusion of donor apoptotic splenocytes

Objective To investigate the effect of transfusion of allogeneic apoptotic splenocytes on immunological tolerance to pancreatic islets transplantation in rat. Method Recipient SD rats were rendered diabetic mellitus by a single intraperitoneal injection of streptozotocin (STZ). The apoptosis of donor Wistar rat splenocytes was induced by X-irradiation with electron linear accelerator. Pancreatic islets were isolated by intraductal collagenase P, and were purified by Ficoll-400 discontinuous density gradient after culturing for 1-2 days from donor Wistar rat. The diabetic SD rats were randomly divided into 4 groups, and respectively received infusion of Hanks solution, donor normal splenocytes, donor apoptotic splenocytes, and donor necrotic splenocytes via dorsal veins of penis, and then they received pancreatic islets from the same donor rat underneath their renal subcapsular space 7 days later. Mixed lymphocyte reaction (MLR) was used as immunological parameter of transplantation tolerance besides the observation of blood glucose level and allograft survival time. Islet graft failure was defined as the presence of a plasma glucose concentration of at least 11.0mmol/L on 2 successive days. Results The pre-infusion of donor apoptotic splenocytes significantly prolonged the survival time of allograft as shown by the median survival time (MST) of graft of 31days, and the longest survival time of 42 day, and it apparently decreased the rejection response in recipient SD rat in one-way mixed lymphocyte culture. Conclusion Transfusion of donor apoptotic splenocytes could induce immunological tolerance of allogenic islets transplantation in rat.