小鼠同种异基因骨髓移植aGVHD动物模型的建立_临床医学论文.docVIP

小鼠同种异基因骨髓移植aGVHD动物模型的建立_临床医学论文 小鼠同种异基因骨髓移植aGVHD动物模型的建立_临床医学论文 【摘要】 目的 ：建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation， Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease，aGVHD)动物模型，为Allo-BMT中aGVHD研究提供理想的实验平台。方法：以雄性C57BL/6(H-2b)为供鼠，雌性BALB/C(H-2d)为受鼠，受鼠致死性全身照射(total body irradiation，TBI)(8.0 Gy)预处理后，在移植物中混合不同比例的供鼠骨髓细胞和脾细胞以引起不同程度的aGVHD。根据存活期、外周血白细胞计数、临床表现及病理检查等判断aGVHD程度。结果：单纯异基因骨髓组只有部分小鼠出现aGVHD，75%的小鼠长期存活(gt;30 d)。混合不同比例的供鼠骨髓细胞和脾细胞的Allo-BMT小鼠出现aGVHD的时间和程度均有差异，其中骨髓与脾细胞1.5:1或1:1混合组小鼠，均可在相对集中的时间内(8～15 d)观察到典型的aGVHD临床和病理改变。结论 ：建立Allo-BMT aGVHD模型需要加入一定比例的脾细胞，供鼠骨髓与脾细胞1.5:1或1:1混合进行的Allo-BMT，可作为理想的aGVHD动物模型。 【关键词】 小鼠;异基因骨髓移植;急性移植物抗宿主病;动物模型 　　Abstract: Objective: To establish a mouse model of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (Allo-BMT) for providing experimental studies of aGVHD. Methods：Male C57BL/6(H-2b)mice were used as donors and female BALB/C(H-2d)mice as recipients.All BALB/C(H-2d) mice were randomly divided into 7 groups and received total body irradiation (TBI) 8.0Gy at 4～6 hours prior to transplantation.Bone marrow cells mixed with spleen cells of donors based upon different proportions were injected into the tail vein.Their survival time，leucocyte counts of peripheral blood，clinical and pathologic manifestations of aGVHD were evaluated.Results：Several mice in the group infused with only bone marrow cells showed insignificant aGVHD evidence，75% mice survived for a long period (gt;30 d). There were significant differences in the incidence and severity of aGVHD with different ratios of bone marrow cells and spleen cells. The groups with co-transplantation of bone marrow cells and spleen cells in ratio of 1.5:1 or 1:1 showed typical clinical and pathological manifestations of aGVHD at a relatively concentrated time(8～15 d).Conclusion ：To establish a mice model of aGVHD needs additional donor’s spleen cells. Infusion of bone marrow cells and spleen cells in ratio of 1.5:1 or 1:1 is perfect as to establish aGVHD