联合氟达拉滨和环磷酰胺的预处理减轻急性移植物抗宿主病的实验研究

Combined fludarabine and cyclophosphamide pretreatment alleviated acute graft-versus-host disease

目的探讨联合氟达拉滨与环磷酰胺的预处理对过继性淋巴细胞植活和急性移植物抗宿主病程度的影响。方法受鼠为8～10周雌性BALB／C小鼠．供鼠为8～10周雄性BALB／C×C57BL／6→F1小鼠。根据预处理方式的不同将受鼠分为5组（n=12）：联合应用氟达拉滨和环磷酰胺组、单用氟达拉滨组、单用环磷酰胺组、全身照射组以及空白对照组即应用生理盐水组。预处理结束后第2天过继性植入5×10^7个供鼠脾细胞，检测供鼠脾淋巴细胞在受鼠外周血中的嵌合率，观察生存时间、急性移植物抗宿主病临床表现。结果联合应用氟达拉滨和环磷酰胺组小鼠的脾淋巴细胞嵌合率与全身照射组相似，急性移植物抗宿主病的临床表现明显减轻（P〈0．05）。结论联合应用氟达拉滨和环磷酰胺能够促进过继性同种异基因淋巴细胞植活，可减轻急性移植物抗宿主病。

Objective To explore the effect of fludarabine combined with cyclophosphamide pretreatment on adoptive lymphocyte engrafment as well as the incidence of acute graft-versus-host disease （GVHD）. Methods Female BALB/C mice of 8 - 10 weeks and male BALB/C × C57BL/6→FI mice of 8 - 10 weeks were divided into five groups according to the pre-treatment methods （n = 12）： fludarabine combined with eyclophosphamide group, fludarabine alone group, cyclophosphamide alone group, total body irradiation （TBI） group and control group. After the pretreatment, 5 × 10^7 donor mouse spleen cells were engrafted, and the chimerism of doner lymphocytes, the survival time and the manifestations of acute GVHD were observed. Results Compared with the TBI group, the fludarabine and cyclophosphamide group had a similar splenocytes chimeric rate, while the incidence of acute GVHD were significantly decreased （P〈0. 05 ）. Conclusions Combination of fludarabine and cyclophosphamide can promote adoptive allogeneic lymphocytes engrafment while alleviate acute graft-versus-host disease.