骨髓移植诱导大白兔特异性免疫耐受模型的建立

发布时间：2018-05-08 15:18

本文选题：骨髓移植 + 特异性免疫耐受　；参考：《江西医学院》2005年硕士论文

【摘要】：[背景及目的]:近年来,采用造血干/祖细胞移植形成供受者混合嵌合诱导特异性免疫耐受成为免除器官移植排斥反应的一个新方法。混合型嵌合状态是供受者造血干细胞同时存在而不相互排斥的现象, 若要建立这种状态,骨髓移植前的预处理和造血干细胞的采集数量是能否形成混合嵌合的关键,目前,在小鼠动物模型实验中,通过采用低毒性非清髓的预处理方案,已经成功诱导了皮肤等器官的特异性耐受。对免疫耐受的诱导来说,形体越大、进化程度越高的动物,特异性免疫耐受越难诱导,是否能在更高级别的动物模型中成功诱导特异性免疫耐受呢?在本实验中,我们以新西兰大白兔作为动物实验模型,受者全身照射预处理后,通过供体与受体的骨髓移植来诱导受体对供体的特异性免疫耐受,在进行骨髓移植的同时进行皮肤移植,观察同种皮肤移植的成活情况,旨在证明,以大白兔这种较大形体的啮齿类作为动物实验模型,也可实现通过骨髓移植来诱导同种异体移植免疫耐受的结果,为同种组织器官移植排斥反应的预防提供理论依据。 [方法]:30 只雄性和30 只雌性新西兰大白兔分别作为供者和受者,随机配对,将30 对大白兔再随机分为5 组,即无处理对照组、单纯照射组、单纯骨髓移植(BMT)组、实验组(照射+BMT)和无关皮肤供体对照组,每组6 对。受者给予7Gy 的全身照射(TBI),24 小时后耳缘静脉输注骨髓单个核细胞,5 天后再次回输相同供者的骨髓单个核细胞,两次总的细胞数量为1～1.5×108/kg,在第二次回输细胞的同时,移植皮肤。观察皮肤移植存活时间、对第三方皮肤的排斥反应及对供体的单向混合淋巴细胞反应,并用多聚酶链式反应(PCR)检测嵌合体的形成。 [结果]:单纯照射和骨髓移植不能延长移植物的存活时间,也没有形成供受者混合嵌合;实验组皮肤移植物存活时间(45.83±3.97d)比无处理对照组(10.83±0.75)、单纯照射组(12.5±1.0488)、单纯骨髓移植组(11.33±0.8165)、无关皮肤供体对照组(12.17±1.169)明显延长(P
[Abstract]:[background and purpose]: in recent years, the use of hematopoietic stem / progenitor cell transplantation to form donor mixed chimerism induced specific immune tolerance has become a new method to avoid rejection of organ transplantation. Mixed chimerism is the phenomenon of donor hematopoietic stem cells at the same time without mutual rejection. To establish this state, before bone marrow transplantation The preconditioning and the collection of hematopoietic stem cells is the key to the formation of mixed chimerism. At present, in the mouse model experiment, the specific tolerance of the skin and other organs has been successfully induced by the use of low toxic non myeloamedullary pretreatment scheme. For immune tolerance, the larger the body and the higher the evolution degree, the higher the animal, the higher the degree of evolution. The more difficult the heterosexual immune tolerance is to induce, is it possible to induce specific immune tolerance in a higher animal model? In this experiment, we used New Zealand white rabbits as animal experimental models, and the recipients were pretreated with the donor and receptor bone marrow to induce the specific immune tolerance of the recipient to the donor. The survival of the same skin graft was observed at the same time as bone marrow transplantation and the survival of the same skin graft was observed. It was designed to prove that the large form of rodents, such as the rabbits, could be used as animal experimental model, and the results of allograft immune tolerance could be induced by bone marrow transplantation, and the prevention of allograft rejection of allograft tissues was provided. Theoretical basis.
[method]: 30 male and 30 female New Zealand white rabbits were randomly paired as donors and recipients, and 30 pairs of rabbits were randomly divided into 5 groups, that is, no treatment control group, simple irradiation group, simple bone marrow transplantation (BMT) group, experimental group (irradiation +BMT) and unrelated skin donor control group, 6 pairs in each group. The recipients were given full body irradiation of 7Gy (TBI). 24 hours later, the bone marrow mononuclear cells were injected into the auricular vein, and the bone marrow mononuclear cells of the same donor were retransfused again after 5 days. The total number of the two total cells was 1 to 1.5 x 108/kg, and the skin was transplanted at the same time of second retransmission of the cells. The survival time of the skin transplantation, the rejection of the third skin and the one way mixed lymph node to the donor were observed. Cell reaction and polymerase chain reaction (PCR) were used to detect the formation of chimeras.
[results]: the survival time of the graft was not prolonged by simple irradiation and bone marrow transplantation, and no donor chimerism was formed. The survival time of the skin graft in the experimental group was (45.83 + 3.97d) than that in the non treated control group (10.83 + 0.75), the simple irradiation group (12.5 + 1.0488), the simple bone marrow transplantation group (11.33 + 0.8165), and the skin donor control group (12.17 + 1.). 169) obviously lengthening (P

【学位授予单位】：江西医学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R-332

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