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随着2000年Edmonton方案提出并应用到胰岛移植后,使得移植的成功率大大提高。该方案之所以取得极大的成功,其中尤为重要的是其对以往的免疫抑制方案的改进,这使得免疫耐受的诱导成为近年来胰岛移植领域的研究热点之一。首先新型免疫抑制药物,如脱氧精胍菌素、来氟米特等,在延长同种异体胰岛移植的存活时间的同时,且无任何β细胞毒性作用,提高了胰岛移植的成功率。其次,通过TNF/TNFR家族和B7/CD28家族共刺激分子的阻断,同样具有相似的效果,抗CD40L抗体和CTLA-4 Ig诱导移植免疫耐受已经进入临床研究阶段。而通过调节细胞因子网络(如IL-4、IL-6和IGF)干预Thl/Th2转换亦可诱导移植耐受,但孤立的细胞因子治疗并不足以诱导耐受发生和维持。而让胰岛细胞表达可抑制细胞凋亡基因,同样对移植物功能存活具有重大意义,研究表明Fas/FasL、DCR3和A20基因等均能对移植胰岛的存活起保护作用。随着研究的深入和免疫学的发展,将对免疫耐受的机制有更为深人地了解,相信在未来的胰岛移植治疗糖尿病领域,移植排斥现象将能得到高效可靠的解决方法。
With the 2000 Edmonton program put forward and applied to islet transplantation, making the success rate of transplantation greatly improved. The program has achieved great success. Especially important is its improvement on previous immunosuppressive regimens, which makes the induction of immune tolerance one of the hot topics in the field of islet transplantation in recent years. First, new immunosuppressive drugs, such as deoxyspergualin, leflunomide and so on, to extend the survival time of allogeneic islet transplantation, and without any β-cell toxicity, increased the success rate of islet transplantation. Second, the blocking of co-stimulatory molecules by the TNF / TNFR family and the B7 / CD28 family also had similar effects. Immune tolerance induced by anti-CD40L antibodies and CTLA-4 Ig has entered the clinical stage. Transplant tolerance can also be induced by the intervention of Thl / Th2 transitions through the regulation of cytokine networks (eg IL-4, IL-6 and IGF), but isolated cytokine therapy is not sufficient to induce tolerance to development and maintenance. However, the expression of islet cells can inhibit the gene expression of apoptosis, the same function of graft survival is of great significance, studies have shown that Fas / FasL, DCR3 and A20 genes can all play a protective effect on the survival of transplanted islets. With the deepening of research and the development of immunology, we will have a deeper understanding of the mechanisms of immune tolerance. We believe that in the future of islet transplantation for the treatment of diabetes, transplant rejection can be efficiently and reliably solved.