不同照射剂量对急性移植物抗宿主病小鼠模型建立的影响  

Effect of different irradiation doses on establishment of murine acute GVHD model after MHC-mismatched transplantation

作　　者：惠玉[1,2] 刘元林[2] 陈秀慧[3] 马士凤[4] 于洋[2] 王洋[2] 李雪[2] 周凡[5] 张毅[2] 

机构地区：[1]辽宁医学院沈阳军区总医院研究生培养基地,沈阳110016 [2]军事医学科学院基础医学研究所细胞生物学研究室,北京100850 [3]河北北方学院研究生部,河北张家口075000 [4]天津医科大学总医院儿科,天津300052 [5]沈阳军区总医院,沈阳110016

出　　处：《军事医学》2016年第2期122-126,共5页Military Medical Sciences

基　　金：国家自然科学基金面上资助项目(31070996;31171084)

摘　　要：目的探讨不同预处理照射剂量对主要组织相容性复合体（major histocompatibility complex,MHC）不相合造血干细胞移植后急性移植物抗宿主病（acute graft-versus-host disease,a GVHD）小鼠模型建立的影响。方法选择C57BL/6（H-2b）→BALB/c（H-2d）作为完全异基因移植的供体和受体。根据60Coγ射线照射剂量的不同,将受体鼠分为7.0、8.0和9.0 Gy照射组。受体鼠经60Coγ射线全身照射4～6 h后,输注供体鼠的骨髓细胞（1×107/只）和脾细胞（1×107/只）,观察移植后各组小鼠的一般状态、外周血白细胞计数、生存率、靶器官（肝、小肠）的病理学变化,判断a GVHD小鼠模型是否建立。结果照射剂量7.0 Gy的小鼠一般状态好,a GVHD的症状和体征不典型,全部存活。8.0和9.0 Gy照射小鼠表现出典型的a GVHD症状和体征,移植后早期死亡率高,Cooke评分高,8.0Gy照射小鼠生存率为50%,而9.0 Gy照射小鼠均死于造血衰竭。组织病理学结果显示,8.0或9.0 Gy小鼠的靶器官（肝、小肠）损害程度较其他组严重。结论照射剂量对诱导小鼠a GVHD的发生至关重要,选择合适的照射剂量可建立高效稳定的小鼠a GVHD模型。Objective To investigate the effect of different doses of irradiation on the establishment of a murine acute graft-versus-host disease（ aGVHD ） model after major histocompatibility complex （ MHC ） -mismatched hematopoietic stem cell transplantation. Methods C57BL/6 （H-2b） And BALB/c （H-2d） mice were chosen as donors and recipients respec- tively. The recipients were randomly divided into three groups and received total body irradiation （TBI） of 60Co γ ranging from 7.0, 8.0 to 9.0 Gy,respectively. After TBI for 4 -6 hours, the donors＇ bone marrow （1 × 10^7/mouse） and splenic cells （1 ×10^7/mouse） were transplanted into the recipients. The clinical signs, WBC, survival rate, damage to target or- gans and histopathologieal alteration of these mice were evaluated to test the murine aGVHD model. Results Recipients that received TBI of 7.0 Gy exhibited non-significant aGVHD symptoms and both of them survived. Recipients that received TBI of 8.0 and 9.0 Gy exhibited significant aGVHD symptoms, a higher mortality and Cooke score soon after the transplan- tation. The irradiation dose of 8.0 Gy resulted in a lower survival rate of 50% while the recipients that received an irradia- tion dose of 9.0 Gy died of hematopoiesis failure. Furthermore, both groups exhibited more severe target organ damage. Conclusion The irradiation dose has a direct effect on the establishment of a murine aGVHD model so that optimization of the irradiation dose can help to establish the model.

关 键 词：小鼠 模型 动物 辐射剂量 急性移植物抗宿主病 主要组织相容性复合物 

分 类 号：R457.7[医药卫生—治疗学]