EL4T淋巴细胞白血病／淋巴瘤小鼠急性移植物抗宿主病动物模型的建立  

Establishment of an acute graft-versus-host disease animal model in EL4 T-cell leukemia/lymphoma mice

作　　者：张琳[1] 殷丽萍[1] 高洋[1] 韩美园[1] 陆超[1] 

机构地区：[1]南京医科大学第一附属医院儿科,210029

出　　处：《中华实用儿科临床杂志》2013年第3期183-187,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81170487）

摘　　要：目的建立EL4T淋巴细胞白血病／淋巴瘤小鼠急性移植物抗宿主病（acute graft-versus-host disease, aGVHD）的动物模型，为同种异基因骨髓移植（allogeneic bone marrow transplantation, Allo-BMT）中防治aGVHD和保留移植物抗白血病（graft—versus—leukemia，GVL）研究提供理想的模型。方法以雄性BALB／c（H-2Kd）小鼠为供鼠，雌性C57BL／6（H一2Kb）小鼠为受鼠，受鼠致死性全身照射（9．5Gy）预处理后，进行Allo—BMT。用随机数字法将受者分为3组，每组17只。（1）单纯照射组：经受着尾静脉输注RPMI1640培养液（0．2mL／只）；（2）aGVHD组：每经尾静脉输注供鼠骨髓细胞（5×10^6个／只）＋脾细胞（5×10^6个／只）；（3）EIAT淋巴细胞白血病／淋巴瘤aGVHD组：经尾静脉输注供鼠骨髓细胞（5×10^6个／只）＋脾细胞（5×10^6个／只）＋EL4细胞（500个／只）。观察受鼠的一般情况、生存期，记录GVHD和白血病发生情况，行组织病理学、免疫组织化学和嵌合体检查。结果单纯照射组小鼠平均生存时间为（10．10±0．43）d，aGVHD组小鼠平均生存时间（28．12±5．01）d，EL4T淋巴细胞白血病／淋巴瘤aGVHD组小鼠平均生存时间为（31．05±5．48）d。aGVHD组和EL4T淋巴细胞白血病／淋巴瘤aGVHD组小鼠平均生存时间均显著长于单纯照射组（P均〈0．01），aGVHD组与EL4T淋巴细胞白血病／淋巴瘤aGVHD组比较差异无统计学意义（P〉0．05）。aGVHD组和EL4T淋巴细胞白血病／淋巴瘤aGVHD组小鼠皮肤、肝脏和小肠病理切片存在GVHD病理改变，EL4T淋巴细胞白血病／淋巴瘤aGVHD组小鼠肝脏、脾脏组织病理切片均存在白血病细胞浸润表现。结论EL4T淋巴细胞白血病／淋巴瘤小鼠aGVHD的动物模型是可靠的，可作为理想的aGVHD动物模型。Objective To establish an acute graft-versus-host disease （aGVHD） model in EL4 T-cell leukemia/lymphoma mice, for providing experimental model to prevent aGVHD while maintaining graft-versus-leu1 mia （GVL） effect during allogeneic bone marrow transplantation （Allo-BMT）. Methods Male BALB/c （H-2Kd）mice were used as donors and female C57BL/6（H-2Kb） mice were used as recipients. C57BL/6 hosts were given 9.5 Gy lethal total body irradiation at 4 hours prior to transplantation. Mice were randomly assigned into 3 groups and each group contained 17 recipients：The recipients in radiation group were injected with 0.2 mL RPMI 1640 as control. The recipients were injected with donor bone marrow cells （5 ×10^6/mouse） and splenocyte for aGVHD（5 x 106/mouse）. The recipients in EIA T-cell leukemia/lymphoma aGVHD group were injected with donor bone marrow cells （5 ×10^6/mouse） and plus 500 EIA cells （5 ×10^6/mouse） . General state,life span and histopathology of the recipient mice and detected chimera were observed. Results The results showed that the mean survival time in radiation group was （ 10.10 ± 0. 43 ） days, in aGVHD group was（28.12 ± 5.01 ）days, in EL4 T-cell leukemia/lymphoma aGVHD group was （31.05 ± 5.48 ） days. The mean survival time in aGVHD group and EL4 T-cell leukemia/lymphoma aGVHD group were significantly longer than that in radiation group （all P 〈 0.01 ） , but there was no significant difference between aGVHD group and EL4 T-cell leukemia/lymphoma aGVHD group （ P 〉 0.05 ）. Histopathological analysis in several target organs （skin,liver and small intestine） confirmed the presence of sever GVHD in aGVHD group and EL4 T-cell leukemia/ lymphoma aGVHD group. Pathological examination showed disorganization of normal tissues and leukemic cell infiltration in EIA T-cell leukemia/lymphoma aGVHD group. Conclusion The EL4 T-cell leukemia/lymphoma aGVHD mice model is reliable to the experimental research of aGVHD.

关 键 词：急性移植物抗宿主病 同种异基因骨髓移植 小鼠 动物模型 

分 类 号：R733[医药卫生—肿瘤] R-332[医药卫生—临床医学]