小鼠移植物抗宿主病模型的建立及其初步应用

ESTABLISHMENT OF MURINE GRAFT-VERSUS-HOST DISEASE MODEL AND ITS PRELIMINARY APPLICATION

建立小鼠GVHD模型 ,用以评价人CD4 0 Ig融合蛋白治疗的有效性。以雄性C5 7BL/ 6小鼠作为脾细胞供者 ,照射后的雌性BALB/c小鼠作为受者 ,分别将 2 5×10 7和 5 0× 10 7/L脾细胞在60 Co射线亚致死剂量照射后经尾静脉注入 30只受者小鼠体内 ,建立小鼠GVHD模型。然后 ,在GVHD诱导后第 0、2、4天分 3次经尾静脉注射CD4 0 Ig融合蛋白各 5 0、15 0、4 5 0 μg,观察CD4 0 Ig融合蛋白对GVHD小鼠的治疗效果。结果显示 :3注射脾细胞 4～5天后 ,小鼠开始出现GVHD典型体征 ,第 10天受体小鼠体内扩增出雄性供体小鼠Y染色体特异片段。CD4 0 Ig融合蛋白治疗可显著延长GVHD小鼠的平均存活时间。此结果表明 ,已成功地建立了小鼠GVHD模型 ,可用于评价抗GVHD的治疗效果。

To establish murine graft versus host disease (GVHD) model, in order to evaluate the efficacy of human CD40 Ig fusion protein treatment. To establish murine GVHD model, 2 5×10 7 or 5 0×10 7 /L spleen cells of male C57BL/6 mice were intravenously injected into female BALB/c mice, as receipt, respectively, after sub lethally irradiation by 60 Co source. After the induction of GVHD, human CD40 Ig fusion protein was intravenously injected three times at a dose of 50μg, 150μg and 450μg on day 0, 2 and 4, respectively. The results showed that the typical expressions of GVHD were observed 4 or 5 days after the injection of donor spleen cells, and specific male Y chromosome fragment was amplified by genomic PCR in female BALC/c receipts. The mean survival time (MST) of GVHD induced mice was significantly prolonged by the treatment of human CD40 Ig fusion protein. It is suggested that Murine GVHD model successfully established can be used in evaluating the effects of anti GVHD therapies.