mPEG修饰移植物中T细胞表面抗原对异基因骨髓移植的影响

发布时间：2018-05-13 12:25

本文选题：甲氧基聚乙二醇 + 化学修饰　；参考：《中国人民解放军军医进修学院》2005年硕士论文

【摘要】：背景:移植物抗宿主病(GVHD)是异基因骨髓移植重要并发症,其原因是供者骨髓中成熟T淋巴细胞攻击受者脏器细胞所致。GVHD与移植物抗白血病作用(GVL)有一定关联,防治GVHD的方案多数可造成GVL作用削弱。甲氧基聚乙二醇(mPEG)是一种无免疫原性的化学修饰物,能够不同程度地遮蔽T细胞表面的抗原,减轻被修饰物的免疫原性。目的:分析mPEG修饰供者骨髓T细胞表面抗原后,是否减轻异基因骨髓移植中GVHD反应,同时观察对GVL作用的影响。方法:实验1.受鼠BABL/c~(H-2d)小鼠照射后随机分为三组,未修饰移植组经尾静脉输入未被mPEG修饰的异基因供鼠615~(H-2k)小鼠骨髓和脾细胞悬液(BMS),修饰移植组输入mPEG修饰的BMS,观察两组间GVHD反应的差别;实验2.杂交一代小鼠(BALB/c~(H-2d)×615~(H-2k))F_1随机分为四组,除照射组外其余三组均经腹腔接种同等剂量的白血病细胞。3天后四组小鼠一同进行照射。然后修饰组和未修饰组分别移植mPEG修饰和未修饰的亲代BABL/c~(H-2d)小鼠骨髓和脾细胞,比较两组间GVL作用的差别。结果:实验1.未修饰组在+4天后出现脱毛等表现,75%为中重度;修饰组+7天后出现相同表现,中重度病例为35%,两组中重度病例比较X~2=6.465,P=0.011。未修饰组小鼠30天存活率15%,修饰组为50%(X~2=5.584,P=0.018);未修饰组
[Abstract]:Background: graft-versus-host disease (GVHD) is an important complication of allogeneic bone marrow transplantation. GVHD is associated with graft versus leukemia (GVLL). Most of the programs of preventing and treating GVHD can weaken the function of GVL. Methoxy poly (ethylene glycol) (mPEG) is a non-immunogenicity chemical modifier which can shield the antigen on T cell surface to some extent and reduce the immunogenicity of the modified substance. Aim: to investigate whether mPEG modified donor bone marrow T cell surface antigen can attenuate the response of GVHD in allogeneic bone marrow transplantation and to observe the effect of GVL on it. Methods: experiment 1. Irradiated mice were randomly divided into three groups. In the unmodified transplantation group, bone marrow and spleen cell suspensions were injected into the bone marrow and spleen cell suspension of the mice without mPEG modification via caudal vein, and the difference of GVHD reaction between the two groups was observed in the modified transplantation group. The first generation of hybrid mice were randomly divided into four groups. The other three groups were irradiated with the same dose of leukemic cells inoculated intraperitoneally for 3 days. Then the bone marrow and spleen cells of mPEG modified group and unmodified group were transplanted into bone marrow and spleen cells of mPEG modified group and unmodified parent group respectively. The difference of GVL effect between the two groups was compared. Results: experiment 1. After 4 days, 75% of the unmodified group showed hair loss and 75% of the modified group showed the same symptoms after 7 days, and the moderate and severe cases were 35%. The comparison between the two groups of moderate and severe cases was made between the two groups. The 30-day survival rate of mice in the unmodified group was 15 days, and that in the modified group was 55.584P0.018; in the unmodified group, it was 5.584; in the unmodified group, the survival rate was 0.018.
【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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