AIM: To establish an acute graft - versus - host disease ( GVHD ) model in EL9611 erythroleukemia mice.METHODS: Using C57BL/6 ( H - 2b ) mice as the donor and BALB/c ( H - 2d ) mice as the recipient in allogeneic bone marrow transplantation ( allo - BMT ), the acute GVHD model was established.The mice were divided into leukemia group ( n = 10 ), radiation control group ( leukemic mice given radiation without allo - BMT, n = 4 ), GVHD group ( leukemic mice given radiation + allo - BMT, n = 10 ) and normal control group ( n = 4 ).In leukemia group, 2 × 106/mouse EL9611 erythroleukemic cells were transfused via tail vein into BALB/c mice to build the erythroleukemia model.In GVHD group, 7 days after leukemic cell transfusion, the mice received total dose of 8.0 Gy [60Co]γ of total body irradiation( TBI ), and within 5 h, 2 × 10 C57BL/6 bone marrow cells and 1 × 10 C57BL/6 spleen cells per mouse were transfused via tail vein to build the acute GVHD model in EL9611 erythroleukemia mice.The clinical manifestations of posture , fur, stool and so on were observed.Pathological examination was conducted to examine the changes of liver, spleen, skin, small intestine and peripheral blood.The survival rate was also calculated.RESULTS: ( 1 ) In leukemia group, the mean survival time ( MST ) was ( 14.5 ± 2.1 ) days, or ( 7.5 ± 0.7 ) days when irradiation day was as day 0( P ＜ 0.01 compared with GVHD group ).The death rate was 100％ with no spontaneous remission.The dead mice showed splenohepatomegalia [liver weight ( 2.40 ±0.48 ) g, spleen weight ( 0.84 ±0.20 ) g, P ＜0.01 compared with normal group]and high WBC count [( 3.33 ±0.27 ) × 1010/L prior to death, P ＜0.05, compared with normal group].Pathological examination showed disorganization of normal tissues and leukemic cell infiltration.( 2 ) In radiation control group, MST was ( 9.0 ± 0.7 ) d, with significant difference as compared with GVHD group and normal group ( P ＜ 0.01 ).The death rate was 100％.Pathological examination showed hematopoiesis exhaustion.( 3 ) In GVHD group, MST was ( 32.0±3.2)d(P＜ 0.01 compared with other groups ).The death rate was 100％ , the symptoms were observed on day 10 - 13 after allo-BMT.Clinical manifestations and pathological examination corresponded to those of Ⅰ degree to Ⅱ degree of GVHD.CONCLUSION: Intravenous infusion of 2 × 106/mouse EL9611 leukemic cell successfully establishes the EL9611 erythroleukemia animal model.Seven days after EL9611 leukemic cell transfusion, lethal dose of TBI and allo - BMT can successfully build the acute GVHD model of EL9611 leukemic mice.%目的:建立EL9611红白血病小鼠急性移植物抗宿主病(GVHD)的动物模型.方法:同种异基因骨髓移植(allo-BMT)以C57BL/6(H-2b)鼠为供鼠,BALB/c(H-2d)为受鼠.设白血病组(n=10)、照射对照组(白血病鼠照射后不进行allo-BMT,n=4)、GVHD组(白血病鼠照射+allo-BMT,n=10)及正常对照组(n=4).白血病组采用每只BALB/c鼠尾静脉输注2×106个EL9611红白血病细胞建立红白血病动物模型;GVHD组于接种白血病细胞7 d后行总剂量为8.0 Gy的1次性[60Co]γ射线全身照射(TBI),照射后5 h内每只小鼠尾静脉输注C57BL/6鼠骨髓细胞2×106个+脾细胞1×107个,建立EL9611红白血病小鼠的急性GVHD动物模型.观察小鼠体位、皮毛、大便等临床表现,病理检查肝脾、皮肤、小肠、外周血和骨髓,计算生存率.结果:白血病组生存时间(14.5±2.1) d[从照射当天(第0 d)算起为(7.5±0.7) d],生存时间与GVHD组相比P<0.01,死亡率100%,无自发缓解,死亡时肝脾肿大(肝重2.40 g±0.48 g,脾重0.84 g±0.20 g,与正常对照组比P<0.01),外周血WBC升高[死亡前(3.33±0.27)×1010/L,与正常对照组比P<0.05],病理检查示组织正常结构破坏,白血病细胞浸润.照射对照组生存时间为(9.0±0.7) d,生存时间与GVHD组和正常对照组相比差异显著(P<0.01),死亡率100%,病理检查显示造血衰竭.GVHD组生存时间为(32.0±3.2)d,生存时间与其它各组相比P<0.01,死亡率100%,allo-BMT后第10-13 d出现症状,临床表现和病理检查符合Ⅰ到Ⅱ度GVHD的改变.结论:采用EL9611红白血病细胞(2×106/鼠)静脉输注的方式可成功建立EL9611红白血病动物模型;接种EL9611红白血病细胞第7 d行TBI +allo-BMT可成功建立EL9611红白血病小鼠的急性GVHD动物模型.
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