BRD4信号通路阻断诱导小鼠移植心脏耐受机制研究

在有限的器官供体数量前提下，促进移植耐受诱导一直是临床器官移植的一个重点。本研究基于先前器官移植工作基础上，进一步利用小分子化合物JQ1对BRD4信号通路特异性阻断后诱导小鼠移植心脏耐受的机制探索，本课题拟在小鼠心脏移植模型上，研究分析免疫细胞、各种炎性相关的细胞因子（HMGB1、IL-6、IL-1beta、TNF-alpha、IL-10等）表达、心肌组织结构重塑情况，以及验证所获得的移植耐受特异性、感染性，前瞻性探索BRD4信号通路阻断和其它免疫耐受诱导剂联合应用后对延长移植心脏存活的影响，为改善和解决临床上心脏移植受体的治疗提供新的治疗策略。

Owing to the limited amount of donated organs, improvement of transplant tolerance is always a clinical challenge. After our past studies on pro-inflammatory cytokines IL-6 and immune cells in organ transplantation, we further revealed that blockade of BRD4 signaling pathway by novel compound JQ1 could significantly prolong mice cardiac allograft survival. By using mice cardiac transplant model, our present study would deeply investigate the underlying mechanisms on immune cells, profiling of inflammation-related cytokines (HMGB1, IL-6, IL-1beta, TNF-alpha, IL-10, etc.), cardiac remodeling. Its specificity and infectious feature will be further tested. In addition, the combination of blockade of BRD4 signaling pathway and other tolerogenic agents will be utilized to induce transplant tolerance. Our study would provide new therapeutic strategy for cardiac transplantation.