摘要
目的：探讨新型免疫抑制药物雷帕霉素（RAPA）对小鼠异基因骨髓移植（allo-BMT）后急性移植物抗宿主病（aGVHD）的抑制作用，并与传统免疫抑制药物比较作用效果。方法：用主要组织相容性抗原（MHC）完全不合的纯种近交系小鼠[供鼠为雄性c57BL／6J（H-2“）鼠，受鼠为雌性BALB／c（H-2^d）鼠]建立allo-BMT／aGVHD动物模型，随机分5组，第1、2和3组分别给予RAPA、环孢菌素A（CsA）加甲氨蝶呤（MTX）、RAPA加CsA加MTX联合用药作为aGVHD抑制方案，第4组为空白对照，第5组为未移植组。观察各组小鼠骨髓移植后aGVHD的出现情况。结果：移植小鼠出现典型的aGVHD症状，未用aGVHD预防方案的移植小鼠（第4组）死亡高峰在移植后第5～7天，死亡率达100％。用不同aGVHD预防方案的第1～3组小鼠aGVHD症状明显减轻，平均生存时间（MST）较第4组显著延长（分别延长3．5、1．9和6．0d，P〈0．05）。不同aGVHD预防方案的移植小鼠之间，移植后外周血常规变化差异无显著性。经用各预防方案后，移植小鼠aGVHD病理表现减轻，且RAPA、CsA和MTX联合用药组的病理分级轻于RAPA单药组或CsA加MTX标准方案组。结论：RAPA可以显著抑制体外T淋巴细胞增殖效应，增强小鼠对骨髓移植的免疫耐受，对小鼠骨髓移植后移植物抗宿主病（GVHD）有明显抑制作用，可减轻GVHD症状和病理损害程度，延长平均生存时间。
To evaluate the inhibition effect of rapamycin （RAPA） on acute graft-versus-host disease （aGVHD） after allogeneic hemopoietic stem cell transplantation （allo-HSCT） in a murine model. Methods aGVHD was induced in female BALB/c （H-2d） mice by total-body irradiation （TBI） followed by male allogeneic [ C57BL/6J, （H-2^b） ] bone marrow transplantation, aGVHD was assessed both physically and histologically. Severe aGVHD was developed in the recipients. After allo-HSCT, mice were divided into 5 groups. Group 1 was given RAPA （ 1.5 mg·kg^-1·d^-1） ,group 2 CsA （ 1.5 mg·kg^-1·d^-1） and MTX （0.4 mg·kg^-1·d^-1）, group 3 RAPA in combination with CsA and MTX, group 4 no agents for aGVHD prophylaxis, and group 5 with no transplantation. The physicalsigns, MST, peripheral blood counts, and aGVHD histopathologic examination were observed in all recipients. Results Mice in group 4 developed typical aGVHD and 100 % of mortality, with a mean survival time（MST） of 6 days. The MSTs of group 1 - 3 were significantly longer than that of group 4, being 3.5,1.9,6.0 days longer （ P 〈 0. 05 ）. There was no statistical difference in peripheral blood count among groups 1 -3. Histopathological examination of skin, liver, and gastrointestinal tract showed typical signs of aGVHD in allo-HSCT recipients. Mice received immunosuppressive agents （ RAPA, CsA, MTX） showed the less severe signs. Conclusions RAPA can markedly inhibit T dell proliferative response in vitro and markedly prolong MST of allo-HSCT recipients, delay the onset of aGVHD signs. The prophylaxis effect of CsA plus MTX with RAPA is better than that of RAPA alone. RAPA can decrease GVHD incidence after allo-HSCT in mice.
出处
《东南大学学报（医学版）》
CAS
2008年第2期95-99,共5页
Journal of Southeast University(Medical Science Edition)
基金
江苏省重点学科开放课题(k0613)
关键词
雷帕霉素
移植物抗宿主病
异基因骨髓移植
小鼠
rapamycin
graft-versus-host disease
allogeneic bone marrow transplantation
mice
作者简介
顾炎（1982-），男，江苏南京人，在读硕士研究生，研究方向为异基因造血干细胞移植。通讯作者：丁家华 86-25-83275420
