针对HLA-A2转基因小鼠皮肤移植物的排斥反应更接近急性排斥反应

发布时间：2018-03-21 14:22

本文选题：转基因小鼠　切入点：HLA-A2　出处：《华中科技大学》2009年硕士论文　论文类型：学位论文

【摘要】：同种异型移植排斥反应所识别的靶抗原主要是表达于移植物细胞表面的主要组织相容性复合物(MHc)分子，由于几类主要组织相容性复合物(HLA)基因的丰富多态性，很难在几体水平研究单个异体HLA分子在移植排斥中的具体作用。HLA．A2转基因小鼠的出现为体内研究移植排斥反应机制与干预措施提供了理想的动物模型。本课题以c57BL／6来源的HLA-A2转基因小鼠(以下简称A2小鼠)为主要实验对象，建立仅HLA-A2基因差别所引起的皮肤移植排斥反应动物模型，并通过比较HLA-A2基因差别所引起的移植排斥反应与典型急性排斥反应和慢性排斥反应的异同，探讨这种移植排斥反应的类型与机制。本研究的主要内容及结果如下： 1利用HLA-A2特异性引物RT-PcR及HLA-A2分子特异性抗体BB7.2检测显示HLA-A2转基因小鼠细胞表面表达HLA-A2分子。 2以普通c57BL/6雄性小鼠为受者，雄性A2小鼠为供者，建立仅HLA-A2基因差别所引起的皮肤移植排斥反应动物模型，结果发现针对A2小鼠皮肤移植物的排斥反应发生迅速，9～13天出现皮片排斥反应。将两者脾细胞进行混合淋巴细胞培养结果显示c57BL／6来源的T细胞在体外受A2小鼠的细胞刺激后明显增殖。 3与同种异基因小鼠皮肤移植所引起的急性排斥反应及雌雄异体移植所引起的慢性排斥反应相比较，针对HLA-A2转基因小鼠皮肤移植物的排斥反应及体外同种反应表现出发生迅速，，反应强度大等急性排斥反应的特点。由于供受者之间仅存在HLA-A2的差别，而针对A2小鼠皮肤移植排斥反应更接近急性排斥反应，因此该动物模型可用于进一步认识移植排斥中直接识别机制和探讨移植排斥反应的防治手段。
[Abstract]:The target antigen recognized by allograft rejection is the major histocompatibility complex (MHcc) expressed on the surface of the graft cells, due to the rich polymorphism of several major histocompatibility complexes (HLAs). It is difficult to study the specific role of single allogeneic HLA molecule in transplant rejection at several body levels. The appearance of HLA.A2 transgenic mice provides an ideal animal model for studying the mechanism and intervention of transplantation rejection in vivo. HLA-A2 transgenic mice (A2 mice) were the main experimental objects. To establish an animal model of skin graft rejection caused only by HLA-A2 gene difference, and to compare the difference between transplantation rejection caused by HLA-A2 gene difference and typical acute rejection and chronic rejection. The main contents and results of this study are as follows:. 1 the expression of HLA-A2 on the surface of HLA-A2 transgenic mice was detected by HLA-A2 specific primer RT-PcR and HLA-A2 molecular specific antibody BB7.2. 2C57BL / 6 male mice as recipients and male A2 mice as donors, an animal model of skin graft rejection caused only by HLA-A2 gene difference was established. The results showed that skin graft rejection occurred rapidly in A2 mice after 13 days of skin graft rejection. The mixed lymphocyte culture of both spleen cells showed that the T cells derived from c57BL / 6 were fine by A2 mice in vitro. The proliferation was obvious after stimulation. 3Compared with the acute rejection induced by allogeneic skin transplantation and the chronic rejection caused by male and female transplantation, the skin allograft rejection and in vitro allograft reaction of HLA-A2 transgenic mice showed rapid occurrence. Characteristics of acute rejection with high response intensity. Since there is only a difference between donors and recipients of HLA-A2, the skin graft rejection in A2 mice is closer to acute rejection. Therefore, the animal model can be used to further understand the mechanism of direct recognition of transplant rejection and explore the prevention and treatment of transplant rejection.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392

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