Wang Ming-Hui, Milekhin Vitaliy, Zhang Hua, Huang Hong-Zheng
Department of Nephrology, Essen University Hospital, Essen (45122), Germany.
Acta Pharmacol Sin. 2003 Sep;24(9):847-52.
FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induces long-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present study investigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouse heterotopic cardiac transplantation model.
BALB/c hearts were heterotopically grafted in C57BL/6 mice. FTY720, at the doses of 0.5, 1, and 5 mg.kg-1.d-1 or vehicle was administered to recipients once daily by oral gavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in the peripheral blood and the peripheral lymph nodes were determined on d 5 after transplantation.
FTY720 prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed less lymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered the number of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesenteric lymph nodes and the peripheral lymph nodes.
FTY720 used orally as rescue therapy significantly extended allograft survival in mouse heterotopic cardiac transplantation.
FTY720是一种新型合成免疫抑制剂，其作用机制独特，预防性给药可使大鼠和犬同种异体移植长期接受移植。本研究调查了FTY720是否能够挽救小鼠异位心脏移植模型中正在进行的实体器官移植急性排斥反应。
将BALB/c小鼠心脏异位移植到C57BL/6小鼠体内。在移植后第3天至第7天，通过口服灌胃每天给受体小鼠给予剂量为0.5、1和5mg·kg-1·d-1的FTY720或赋形剂。在移植后第5天测定移植物的组织学变化以及外周血和外周淋巴结中的淋巴细胞数量。
FTY720剂量依赖性地显著延长了移植物的中位存活时间。组织学评估显示，用FTY720处理的心脏同种异体移植物中淋巴细胞浸润较少。此外，FTY720显著降低了外周血淋巴细胞数量，但显著增加了肠系膜淋巴结和外周淋巴结中的淋巴细胞数量。
口服FTY720作为挽救治疗可显著延长小鼠异位心脏移植中同种异体移植物的存活时间。
