静态低温浸泡心脏保存液操作简便、技术成熟、价格低廉，是目前最主要的保存方法，但安全时限较短且尚无一种保存液有绝对优势，故亟待研发一种可长期保存供心的新型保存液。项目组研究发现Nrf2/HO-1信号轴参与线粒体氧化应激、细胞死亡的过程；针对线粒体氧化应激而合作研发的新型SS-Ⅱ保存液，明显上调Nrf2及HO-1表达，抑制DNA损害，发挥心肌保护作用。另发现Nrf2的激活可抑制细胞内ROS的产生及调节活性铁含量，参与了一种崭新的细胞死亡模式--程序性铁坏死。由此申请者提出“SS-Ⅱ保存液可能通过Nrf2/HO-1/Ferroptosis信号轴发挥心肌保护功能”的科学假说，拟制备小鼠腹部异位心脏移植模型并培养原代小鼠心肌细胞，从生理学、细胞学、分子生物学、基因组学和生物信息学等方面进行实验研究，结合临床标本验证，旨在揭示新型SS-Ⅱ保存液对心脏保护的分子机制，为心脏移植领域提供新策略。

With its simple operation, mature technology, low cost and other advantages, static cold soaking preservative solution has taken the lead in organ preservation. But its safety time is short and none of the preservation solutions has absolute advantages. Therefore, it is urgent to develop a new type of preservation solution for long-term preservation of donor heart. Our group discovered that Nrf2/HO-1 signaling pathway participates in mitochondrial oxidative stress and cell death. Furthermore, the new type of SS-Ⅱ preservation solution, developed in response to mitochondrial oxidative stress, could significantly up-regulate the expression level of Nrf2 and HO-1, reduce DNA damage and play a protective role in myocardium. Another study has demonstrated that activation of Nrf2 could suppress cellular ROS generation and regulate reactive iron level, participating in a novel kind of cell death—ferroptosis. Hence, the applicants propose a scientific hypothesis that SS-Ⅱ preservative solution may exert its cardioprotective effects through Nrf2/HO-1/Ferroptosis signal axis. We plan to establish an abdominal heterotopic heart transplantation mice model and culture primary mouse cardiomyocytes, proceeding experimental researches in diverse aspects of physiology, cytology, molecular biology, genomics and bioinformatics. Ultimately, we’ll test these findings with clinical validation. We aim to reveal the underlying molecular mechanism of the cardioprotective effects of SS-Ⅱ preservative solution, thus providing a new clinical treatment strategy in heart transplantation.