新型免疫抑制剂鞘氨醇-1-磷酸受体激动剂研究进展

Research progress in sphingosine-1-phosphate receptor agonist:a novel immunosuppressive drug

免疫抑制剂在器官移植和自身免疫系统疾病的治疗方面疗效显著,但多种不良反应限制了其广泛应用。在寻找高活性、低不良反应的新型免疫抑制剂的过程中发现,鞘氨醇-1-磷酸(S1P)受体激动剂通过使淋巴细胞聚集在淋巴结、脾等次级淋巴器官中,导致血液和胸腺的淋巴细胞减少,同时抑制淋巴细胞进入移植器官中,减少移植排斥反应。因此,通过激动S1P受体阻断淋巴细胞循环可以用于治疗免疫系统疾病。本文主要综述新型免疫抑制剂S1P受体全激动剂和选择性激动剂的特点、作用机制及研究进展。

Objective The clinical application of immunosuppressive drugs in organ transplantation and autoimmune diseases is effective, but a nnmber of adverse effects limit their wider application. In the process of looking for the new immunosuppressive agents with high activity and low adverse reactions, scientists found that lymphocytes gathered through sphingosine-1 -phosphate（ S1 P） receptor agonists in the lymph nodes, spleen and other secondary lymphoid organs, resulting in blood and thymus lymphocyte reduction as well as inhibition of lymphocyte in organ transplantation and reduction of allograft rejection. Therefore, through the activation of the S1 P receptor in the blockade of lymphocyte cycle, S1P receptor agonist can be used as immunosuppressive drugs in the treatment of the immune system diseases. This article reviews the characteristics, mechanism of action and research progress of the new immunosup- pressant S1P receptor agonist and selective agonist.