来氟米特预防小鼠异基因骨髓移植后aGVHD的实验研究

目的 评估来氟米特（LEF）对小鼠异基因骨髓移植（allo-BMT）术后急性移植物抗宿主病（aGVHD）的预防作用.方法 以SPF级雄性C57BL/6（H-2b）为供鼠,雌性BALB/C（H-2d）为受鼠,建立allo-BMT/aGVHD动物模型,并将大鼠随机分为：A组（模型对照组）、B组（环孢菌素A组,剂量为10 mg·kg^-1·d^-1）、C组（LEF组,剂量为10 mg·kg^-1·d^-1）,同时根据临床表现、病理组织学检查、平均生存时间评估各组aGVHD的严重程度.结果 B组和C组受鼠平均生存时间均较A组显著延长（均P〈0.01）,B组和C组间平均生存时间的差异均无统计学意义（均P〉0.05）;B组和C组受鼠的aGVHD临床表现和病理改变均较A组明显减轻.结论 LEF可有效预防小鼠allo-BMT术后出现的aGVHD,并可减轻其症状和病理损害程度,同时显著延长平均生存时间.

Prevention of acute graft-versus-host disease after allogeneic bone marrow transplantation by leflunomide in mice

Objective To evaluate the prevention of acute graft-versus-host disease （aGVHD） after allogeneic bone marrow transplantation （allo-BMT） by leflunomide （LEF） in mice. Methods Acute GVHD was induced in female BALB/C（H-2d） mice by total body irradiation （TBI） followed by transplantation of bone marrow and spleen ceils from male allogeneic C57BL/6 （ H-2b ）. The experiment groups were designed as follows： model control group （group A）, cyclosporine A （CsA 10 mg·kg^-1·d^-1） group （group B ）, LEF （10 mg·kg^-1·d^-1） group （group C）. Severity of aGVHD was assessed by signs of weight loss, diarrhea, ruffled fur, hunched posture, histological changes and mean survival time. Results The mean survival time of LEF group, CsA group were prolonged as compared with that of the model control group （P〈0.01）. aGVHD signs and histological changes of LEF group, CsA group were milder than those of the model control group. There was no significant difference in the mean survival time between the CsA group and LEF group （P〉0.05）. Conclusion LEF is effective in prevention for aGVHD after allo-BMT in mice, it can improve the aGVHD signs and histological changes, markedly prolong mean survival time.