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目的建立主要组织相容性复合物(MHC)相合造血干细胞移植的慢性移植物抗宿主病(Chronic graft versehost disease,cGVHD)小鼠模型,为进一步研究cGVHD的发病机制及防治方法构建平台。方法以雄性DBA/2H-2d为供鼠,雌性BABL/CH-2d为受鼠,接受60Co5.5Gy全身照射后分成3组,4～6h内完成移植。A组输注RPMI1640培养液、B组输注5×107个脾细胞/只、C组输注10×107个脾细胞/只。观察指标为:①造血重建时间;②移植物植入情况;③各组小鼠cGVHD的临床表现;④各组的病理学改变及成模率。结果①造血重建:C组较A、B组造血重建延迟,差异有统计学意义。②植入情况检测:移植组小鼠均为供、受者共存的混合嵌合体。③cGVHD的临床表现及评分:A组均未出现cGVHD的临床表现,B、C组小鼠出现cGVHD的临床表现,两组的临床评分有统计学差异(P=0.016)。④病理改变及成模率:A组病理学未见明显异常;B、C两组出现cGVHD的病理学改变,但是两组评分无统计学差异(P=0.410);根据病理学评分判断各组小鼠的成模率分别为0%、60%、80%。结论 60Co5.5Gy全身照射后输注5×107个脾细胞可诱导出cGVHD小鼠模型,且配型方式与临床MHC相合造血干细胞移植类似,可以作为研究MHC相合造血干细胞移植后cGVHD的理想模型。
Objective To establish a mouse model of Chronic graft versehost disease (cGVHD) with major histocompatibility complex (MHC) and hematopoietic stem cell transplantation (HSC), and to establish a platform for further study on the pathogenesis and prevention and treatment of cGVHD. Methods Male DBA / 2H-2d mice and female BABL / CH-2d mice were irradiated with 60Co5.5 Gy whole body and divided into 3 groups. The transplantation was completed within 4 to 6 hours. Group A was infused with RPMI1640 medium, group B received 5 × 107 splenocytes / group and group C received 10 × 107 splenocytes / group. The observation indicators were: ① hematopoietic reconstruction time; ② graft implants; ③ cGVHD clinical manifestations in mice; ④ pathological changes in each group and the rate of molding. Results ① Hematopoietic reconstitution: Delayed hematopoietic reconstitution was found in group C compared with group A and group B, the difference was statistically significant. ② implantation detection: transplantation group of mice are for the donor coexistence of mixed chimerism. The clinical manifestations and scores of cGVHD: no clinical manifestations of cGVHD were found in group A, while the clinical manifestations of cGVHD in groups B and C were statistically significant (P = 0.016). ④ pathological changes and molding rate: A group of pathological no significant abnormalities; B, C two groups of pathological changes of cGVHD, but there was no significant difference between the two groups (P = 0.410); according to the pathological score to determine the various groups Mice were molded rate of 0%, 60%, 80%. Conclusion 60Co5.5Gy whole body irradiation after transfusion of 5 × 107 splenocytes can induce cGVHD mouse model, and the matching pattern is similar to clinical MHC coincidence hematopoietic stem cell transplantation, which can be used as an ideal model for studying cGVHD after MHC coincidence hematopoietic stem cell transplantation.