板蓝根单体衍生物DIM2抑制器官移植免疫排斥反应的作用及机制研究

现有器官移植免疫抑制剂在免疫抑制效果和毒副作用方面均不够理想，急需开发新型免疫抑制剂。板蓝根单体衍生物2（DIM2）是我们从传统中药板蓝根中筛选的具有免疫抑制活性的单体成分，经化学修饰改良而来的衍生物。在前期研究中，我们证实了DIM2具有良好的免疫抑制活性，结合前期实验，我们推测DIM2可能通过抑制淋巴细胞的周期、诱导调节性T细胞的产生以及影响Th1/Th2平衡来实现的，但其详细的机制尚未阐明。在本研究中我们将系统研究：（1）DIM2抑制淋巴细胞周期的作用和机制；（2）DIM2诱导Treg的作用和机制；（3）DIM2对Th1/2平衡的作用和机制；（4）DIM2联合现有免疫抑制方法诱导免疫耐受。通过上述研究，我们将系统阐明DIM2免疫抑制作用和机制以及诱导耐受的方法，这对促进新型免疫抑制剂的开发和中药资源的保护，以及临床器官移植都有重要的理论和实践价值。

Existing immunosuppressive agents for organ transplantation are not ideal in terms of immunosuppressive effects and side effects, and it is urgent to develop novel immunosuppressive agents. Radix isatidis monomer derivative 2 (DIM2) is a derivative of the monomeric component of immunosuppressive activity that has been selected from the traditional Chinese medicine Radix Isatidis, which has been modified by chemical modification. In the previous study, we confirmed that DIM2 has good immunosuppressive activity. Combined with previous experiments, we speculated that DIM2 may be achieved by inhibiting the lymphocyte cycle, inducing the production of regulatory T cells, and affecting the Th1/Th2 balance, but the detailed mechanism has not yet been elucidated. In this study, we will systematically study: (1) the role and mechanism of DIM2 inhibition of lymphocyte cycle; (2) the role and mechanism of DIM2 inducing Treg; (3) the effect and mechanism of DIM2 on Th1/2 balance; (4) induce immune tolerance with DIM2, in combination with existing immunosuppressive methods. Through the above studies, we will systematically elucidate the immunosuppressive effects and mechanisms of DIM2 and the methods of inducing tolerance, which have important theoretical and practical value for promoting the development of novel immunosuppressive agents, the protection of traditional Chinese medicine resources, and clinical organ transplantation.