器官移植后排斥反应仍未攻克，开发能诱导移植耐受的新型免疫抑制剂迫在眉睫。本课题组长期致力于中药苏木抗心脏移植排斥研究，已证实单体原苏木素A PrA可诱导心脏移植耐受，但仍需继续药效及结构优化以促进临床应用进程。因此前期筛选出更高效低毒的PrA衍生物PrAD并继续明确其药效及机制。为验证lncRNA水平的机制，lncRNA芯片筛选出PrAD诱导移植耐受相关的lncRNA H19，并证实其参与PrAD诱导免疫耐受的作用。本课题组既往已证实miRNA let-7i能诱导耐受性DC及心脏移植耐受，而H19被证实能调控let-7i功能。基于此，我们推测PrAD通过NFκB调控H19转录，H19下游调控let-7i功能诱导耐受性DC及移植耐受。本研究将在分子、细胞、动物及代谢水平证实PrAD的药效及通过H19诱导移植耐受的机制。本课题将推动具有自主知识产权的抗排斥中药的开发，为防治移植排斥提供新策略。

The development of new immunosuppressive agents inducing cardiac transplantation tolerance is a hot spot which is still a tough process.It has been a long time since our group concentrating on Chinese medicine sappan to prevent heart transplant rejection ,during which we have confirmed that prosappaninA(PrA) can induce cardiac transplantation tolerance.However, the potency and structure optimization has to be explored to promote the process of clinical application. In preliminary studies,we screened a more efficient derivative with low-toxicity called PrAD.The high-throughput chip found that the expression of lncRNA H19 is correlated with transplant tolerance ,and we demonstrate H19 mediate the process of PrAD induced immune tolerance. Our previous project point out that miRNA let-7i play an essential role in inducing tolerogenic DC and cardiac transplant tolerance,and H19 is verified can regulate the function of let-7i.Based on this,we confer that PrAD might regulate H19 transcription to induce tolerogenic DC and immune tolerance via NFκB-H19- Let 7i .In this project ,we will demonstrate the mechanism of immune tolerance induced by PrAD, so that we can promote the development of Chinese medicine of anti- rejection to own patent as well as provide new rationales and strategy to prevent immune rejection .