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器官移植的发展取得了令人瞩目的成绩,除了外科技术的日臻成熟外,更为有效、安全的新型免疫抑制剂的不断推出及临床应用起了重要作用。由于移植免疫耐受机制未能弄清,器官克隆,干细胞移植(从细胞→组织→器官→临床应用)到移植临床实际应用尚需经历漫长的道路,因此,21世纪最初的10～15年,器官移植领域依然是免疫抑制为主的时代,但免疫抑制的发展引入了新概念,新趋势。新一代免疫抑制剂使早期移植器官失功的危险性降到最低限度,但同种肾移植长期存活的改善并不乐观。慢性移植肾失功已经成为影响肾脏移植长期存活的最主要因素。此外,移植受者的感染,心血管疾病,免疫抑制剂尤其是calcineurin抑制剂长期应用造成的肝,肾毒性,移植肾血移植肾血管病变及肝功能严重受损,移植后恶性肿瘤的发生等诸多问题,给免疫抑制剂的调控提出了新的课题及要求。未来免疫抑制剂研究与应用的趋势:(1)免疫抑制须建立在对免疫应答的充分理解基础上;(2)尽管许多新型免疫抑制剂在细胞内靶分子作用点的不断完善能产生淋巴细胞特异性免疫抑制作用,而无特异的毒副作用,但免疫抑制的最终目的依然是应当诱导产生/建立供者特异性耐受状态;(3)新型免疫抑制剂应同时保留宿主对病毒、真菌、肿瘤等抗原的免疫反应功能。皮质激素撤除,CNIs的减?
The development of organ transplantation has made remarkable achievements. In addition to the increasingly mature surgical techniques, the continuous introduction of more effective and safe new immunosuppressive agents and their clinical application have played an important role. Due to the failure to understand the mechanism of transplantation tolerance, organ transplantation, transplantation of stem cells (from cells, tissues, organs and clinical application) to the practical clinical application of implants still need to go a long way. Therefore, in the first 10-15 years of the 21st century, The field of organ transplantation is still the era of immunosuppression, but the development of immunosuppression has introduced new concepts and new trends. A new generation of immunosuppressive agents minimizes the risk of organ failure in early-stage transplanted organs, but the improvement in the long-term survival of allografts is not optimistic. Chronic graft failure has become the most important factor affecting the long-term survival of kidney transplants. In addition, graft-versus-host infections, cardiovascular diseases, immunosuppressive agents, especially long-term use of calcineurin inhibitors, cause liver, kidney toxicity, severe graft-versus-host renal allograft disease and impaired liver function, and post-transplant malignancy Many problems, the immunosuppressant regulation proposed new issues and requirements. Future immunosuppressants research and application trends: (1) Immunosuppression should be based on a full understanding of the immune response; (2) Although many new immunosuppressive agents in the target cell molecules continue to improve the point of the ability to produce lymphocytes Specific immunosuppressive effects, but no specific side effects, but the ultimate goal of immunosuppression should still be induced / established donor-specific tolerance status; (3) The new immunosuppressive agents should also retain the host of the virus, fungi, Tumor and other antigens immune response function. Corticosteroid removal, CNIs reduction?