白消安联合环磷酰胺诱导小鼠急性移植物抗宿主病模型的建立  

Establishment of a mouse model of acute graft-versus-host disease by busulfan combined with cyclophosphamide

作　　者：贺信[1] 许晓军[2] 王静[1] 伊文芳[1] 叶永斌[2] 黄宇贤[1] 郭坤元[1] 

机构地区：[1]南方医科大学珠江医院血液内科,广东广州510282 [2]中山大学附属中山医院血液内科,广东中山528403

出　　处：《细胞与分子免疫学杂志》2015年第12期1637-1642,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：广东省科技计划项目[粤科社字(2011)106号];中山市科技计划重大专项(20113A002);中山市科技计划(20122A111)

摘　　要：目的以白消安(BS)联合环磷酰胺(CP)作为移植前预处理方案建立稳定的小鼠急性移植物抗宿主病(a GVHD)模型。方法雄性BALB/c(H-2kd)为受体鼠,雌性C57BL/6(H-2kb)为供鼠,受体鼠接受100 mg/kg BS和200 mg/kg CP预处理后,输入2×107个供鼠的骨髓细胞或2×107个骨髓细胞联合2×107个脾细胞。记录移植后小鼠一般情况,观察a GVHD临床表现,HE染色后检查组织病变情况,流式细胞术检测脾脏、骨髓中细胞嵌合度。结果移植骨髓联合脾细胞组小鼠,移植后7 d开始出现典型a GVHD临床表现,肝、脾、肠、皮肤、肺等组织出现GVHD相关病理形态学改变,并达到完全供者嵌合,中位生存期为10 d,30 d内全部死亡;单移植骨髓细胞组小鼠无a GVHD表现,生存期大于45 d。结论成功建立了稳定可靠的a GVHD小鼠模型,可用于a GVHD的发病机制、防治效果的实验性研究。Objective To develop a stable mouse model of acute graft-versus-host disease（ a GVHD） by preconditioning with busulfan（ BS）-cyclophosphamide（ CP）. Methods Male BALB / c（ H-2kd） as recipients were conditioned with 100 mg / kg BS and 200 mg / kg CP followed by being transplanted with bone marrow cells（ 2 × 107） or bone marrow cells（ 2 × 107）-spleen cells（ 2 × 107） from female C57BL/6（ H-2Kb） as donors. The general data of the transplanted mice were recorded and the manifestations of a GVHD were evaluated. Histopathological changes were observed using HE staining and chimerism in spleen and bone marrow cells was studied using flow cytometry. Results Mice transplanted with bone marrow cells-spleen cells developed classic a GVHD manifestations starting from the 7th day after transplantation with full donor chimerism. GVHD histopathological changes were seen in liver,spleen,intestine,skin and lung of these mice. The median survival time of these a GVHD mice was 10 days,and they all died within 30 days. Mice transplanted with only bone marrow cells survived over 45 days without any a GVHD signs. Conclusion We developed a stable and reliable a GVHD murine model successfully,which can be used to study the pathogenesis,prevention and therapeutic effect of a GVHD.

关 键 词：白消安 环磷酰胺 骨髓移植 急性移植物抗宿主病 医用实验动物学 

分 类 号：R392.4[医药卫生—免疫学] R965[医药卫生—基础医学]