移植物化学修饰后半相合骨髓移植的实验研究  

Effect of chemical modification of grafts on the survival improvement post haploidentical bone marrow transplantation in mice

作　　者：杨光[1] 唐锁勤[1] 张晓飞[1] 刘立真[1] 黄东生[1] 王建文[1] 

机构地区：[1]中国人民解放军总医院小儿内科,北京100853

出　　处：《中华儿科杂志》2004年第9期684-687,i003,共5页Chinese Journal of Pediatrics

摘　　要：目的　研究甲氧基聚乙二醇 (mPEG)修饰移植物对小鼠H 2半相合骨髓移植 (BMT)的影响。方法　以雄性BALB/c小鼠为供鼠 ;雌性CB6F1代小鼠为受鼠 ,随机分为修饰移植、单纯移植和照射对照三组 ,每组各为 2 0只小鼠。三组鼠在致死量60 Coγ射线全身照射后 ,分别由尾静脉注入经mPEG修饰或未修饰的供鼠骨髓细胞和脾细胞 ,观察各组存活率、急性移植物抗宿主病 (aGVHD)的表现、造血恢复情况及存活小鼠的染色体核型。结果　修饰移植组 30天存活率为 75 % ,较单纯移植组(4 0 % )增高 (χ2 =5 0 1,P =0 0 2 5 ) ,而照射对照组 2周死亡率为 10 0 %。修饰移植组血象恢复快于单纯移植组 (P <0 0 5 )。取死亡小鼠的爪垫皮肤、肝及小肠肠管作病理组织学检查 ,修饰组aGVHD病理表现减轻 ,Thomas病理分级轻于单纯移植组。移植后 75天对存活的受鼠进行染色体C带显色法检测嵌合体 ,证实为完全供者型植入。结论　mPEG修饰移植物可明显减轻aGVHD 。Objective Human leukocyte antigen (HLA) haploidentical bone marrow is a potential source of donor to children for its availability. The drawback is deleterious graft versus host disease (GVHD) reaction post transplantation because of the incompatibility of HLA antigen expression between donors and recipients, in which donor T lymphocyte is stimulated to proliferate and differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound without immunogenicity, which was used to modify various proteins covalently and to prepare the versatile blood type. If mPEG modification blocks the activation of T cells in grafts, GVHD reaction probably would become less serious and transplantation might become successful. The aim of this study was to verify the improvement of haploidentical bone marrow transplantation (BMT) in a murine model by using mPEG of certain concentration to modify the grafts. Methods Male BALB/c mice were chosen as the donor, and female CB_6F_1 mice as the recipient. There were three groups of mPEG modification, non-modification and irradiation control, and 20 mice in each group. The modified and non-modified mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to haploidentical lethally irradiated CB_6F_1 mice via the tail vein. After the transplant, (the hematopoietic) recovery, survival rate, acute graft versus host disease (aGVHD) and chromosomal karyotype were analyzed and compared with controls. Results Seventy-five percent (15/20) of mice survived in the group of mPEG modification, while only 40% (8/20) survived in the group without the modification ((χ~2=5.01),P=0.025). And 100% mice died in the group of the irradiation control within 2 weeks. The hematopoietic recovery in the group of mPEG modification was show n to be faster than that in the group without modification (P<0.05). Histopathological examination of the skin, liver and intestine showed typical signs of aGVHD, but the GVHD grading in the group of modification was less severe. The recipi

关 键 词：小鼠 移植物 骨髓移植 GVHD 修饰 存活率 实验研究 PEG ^60Coγ射线 致死量 

分 类 号：R457[医药卫生—治疗学]