器官移植受者HLA-G5表达的初步探讨

发布时间：2018-06-02 23:47

本文选题：人白细胞抗原G + 主要组织相容性复合体　；参考：《中国人民解放军军事医学科学院》2005年硕士论文

【摘要】：HLA-G基因属于MHC非经典Ⅰ类基因,它拥有15个等位基因,能够编码7种不同的蛋白,即HLA-G1～G7,HLA-G1～G4为膜型,HLA-G5～G7为可溶性分子。HLA-G分子通过抑制介导移植物排斥反应的主要效应细胞的功能而发挥作用,如与NK细胞的杀伤抑制性受体(KIR,killed inhibitory receptor)结合从而抑制其杀伤活性、与CD4细胞表面的KIR结合抑制其增殖,HLA-G还以其特有的α3区与CD8细胞结合而诱导其凋亡。因此HLA-G可视为一种免疫耐受诱导分子,在临床上具有潜在的应用前景,对防治和监测器官移植排斥反应具有重要意义。由于可溶性HLA-G5的结构和功能均比较明确,可有效抑制NK细胞杀伤活性、抑制T细胞增殖并诱导活化T细胞凋亡,并且没有抗原特异性,已经成为国外研究的热点之一,而且主要集中在体外模型。鉴于HLA-G5的体外实验环境和体内的微环境存在着很大的差异,无法反应临床中的实际意义,有必要对其体内特性进行研究。本课题从检测移植受者的外周血HLA-G5的表达状况入手,采用酶联免疫吸附法、蛋白印迹法和流式细胞术等方法,探讨了HLA-G5在健康志愿者、肝移植受者、肾移植受者体内表达的异同,HLA-G5与排斥反应发生的关系,施行移植术后HLA-G5的表达情况以及HLA-G5与不同免疫抑制剂使用的关系。同时,对1例心脏移植受者HLA-G5的表达进行动态观察。最后,检测了同一天施行移植术的受者体内的HLA-G5和肿瘤坏死因子家族成员-FasL之间的相关性。研究结果表明:30例健康志愿者中除2例(6.7%)HLA-G5含量分别为8ng/ml和9ng/ml外,其余28例(93.3%)均无HLA-G5的表达;比较50例肝移植受者与30例健康志愿者HLA-G5的表达水平发现,二者在统计学上存在着显著差异性(t=2.6834,P0.01);
[Abstract]:HLA-G gene belongs to MHC nonclassical class I gene. It has 15 alleles and encodes 7 different proteins. That is to say, HLA-G1G _ 7G _ 4 is membrane type HLA-G5G _ 7 as soluble molecule. HLA-G molecule plays a role by inhibiting the function of the main effector cells that mediate graft rejection, such as binding with NK cell killer inhibitory receptor Kir / killed inhibitory receptor to inhibit its killing activity. The inhibition of HLA-G proliferation by binding to KIR on the surface of CD4 cells also induces its apoptosis by binding to CD8 cells with its unique 伪 3 region. Therefore, HLA-G can be regarded as a kind of immune tolerance inducing molecule, which has potential application prospect in clinic, and has important significance in prevention, treatment and monitoring of organ transplantation rejection. Because the structure and function of soluble HLA-G5 are clear, it can effectively inhibit NK cell killing activity, inhibit T cell proliferation and induce T cell apoptosis, and has no antigen-specific, which has become one of the hot research topics abroad. And mainly concentrated in vitro model. In view of the great difference between in vitro experimental environment and in vivo microenvironment of HLA-G5, it is necessary to study its characteristics in vivo. In this study, the expression of HLA-G5 in peripheral blood of transplant recipients was studied by using enzyme linked immunosorbent assay (Elisa), Western blotting and flow cytometry to investigate the expression of HLA-G5 in healthy volunteers and recipients of liver transplantation. The relationship between HLA-G5 expression and rejection, HLA-G5 expression after transplantation and the use of different immunosuppressants in renal transplant recipients. At the same time, the expression of HLA-G5 in one patient with cardiac transplantation was observed dynamically. Finally, the correlation between HLA-G5 and tumor necrosis factor family member-FasL was detected in recipients who underwent transplantation on the same day. The results showed that there was no expression of HLA-G5 in 28 of 30 healthy volunteers except 2 patients with 6. 7% HLA-G5 and the other 28 with 9ng/ml. The expression level of HLA-G5 was found in 50 liver transplant recipients and 30 healthy volunteers. There was significant statistical difference between them.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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