FTY720对小鼠异基因骨髓移植后急性GVHD的预防作用  

Prophylaxis of Acute GVHD after Allogeneic BMT by FTY720 in a Murine Model

作　　者：朱杨[1] 梁辉[1] 

机构地区：[1]上海第二医科大学新华医院血液科,上海200092

出　　处：《上海第二医科大学学报》2005年第8期815-818,共4页Acta Universitatis Medicinalis Secondae Shanghai

摘　　要：目的评估FTY720对小鼠异基因骨髓移植诱发急性移植物抗宿主病(aGVHD)的预防作用。方法36只受体BALB/c小鼠,接受直线加速器一次性全身照射后4～6h内,经尾静脉注射供体小鼠骨髓和脾脏细胞。受体小鼠分为移植方式对照组(A组)和异基因移植治疗组(B组);同时A组分未移植组(A1)、同基因移植组(A2)和异基因移植对照组(A3),B组分CsA5mg/kg组(B1),FTY7200.3mg/kg组(B2)和FTY7201mg/kg组(B3)。移植后受体小鼠,根据生存时间、体重变化和病理组织学检查,评估各组aGVHD严重程度。结果异基因移植各组在移植后第7d造血开始恢复,第14d流式细胞仪检测显示异基因骨髓细胞已植入,病理组织学检查A3组发生重度aGVHD;与B1和B2组比较,B3组aGVHD严重程度最低。结论小鼠异基因骨髓移植后给予FTY720具有预防aGVHD作用,以剂量为1mg/kg时作用显著。Objective To evaluate the prophylactic effect of FTY720 on acute graft versus host disease（aGVHD） after allogeneic bone marrow transplantation（allo-BMT）. Methods Thirty-six recipient BALB/c mice were conditioned with TBI on day 0 and injected i.v. with a cell mixture of bone marrow and spleen made from donor mice. After transplantation, the recipient mice were divided into two groups： group A and group B. Group A consisted of three sub-groups.; no transplantation group （A1） , syngeneic transplantation group （A2） , allogeneic transplantation control group （A3）. Group B had allogeneic transplantation and consisted of three sub-groups： CsA 5 mg/kg group （B1） , FTY720 0. 3 mg/kg group （B2） , FTY720 1 mg/kg group （B3）. Severity of aGVHD could be assessed by the log-rank test of survival time, body weight changes and histological examination. Results In the murine model of allogeneic BMT, hematopoietic reconstitution of recipient mice occurred from dT. Flow cytometric analysis indicated engraftment of allogeneic bone marrow cells on d14. Histological examination showed severe infiltration in the liver, small intestine and skin in allogeneic transplantation control group. The results of log-rank test, body weight changes and histological examination illustrated the severity of aGVHD in B3 group was the lowest. Conclusion FTY720 1 mg/kg is more effective to reduce the severity of aGVHD.

关 键 词：FTY720 急性移植物抗宿主病 异基因骨髓移植 

分 类 号：R96[医药卫生—药理学]