内皮来源多肽EDP3改善心肌缺血再灌注损伤的作用机制研究

心脏缺血再灌注损伤（MIRI）是缺血性心脏病治疗过程中难以避免的病理损伤，也是制约临床再通治疗效果、导致术后心功能衰竭的主要原因，缺乏有效的药物防治手段。EDP3是我们从缺血预处理内皮细胞分泌组分中筛选发现的一条可能由LncRNA lnc-ZBTB16-1:1编码产生的新型多肽，尚未见功能报道。预实验发现，EDP3具有对抗MIRI、减轻心肌氧化损伤的功能；转录组测序结合Western blot验证发现，Nrf2信号通路是其发挥生物功能的关键；已知在心肌细胞中，Nrf2是调控氧化还原平衡、防治MIRI的关键蛋白。课题拟进一步在不同的细胞和动物模型水平，全面论证EDP3对MIRI的防治作用；并通过挽救策略，阐明EDP3的生物来源、论证其调控Nrf2信号通路拮抗MIRI导致的心肌损伤的分子机制。本研究有望为MIRI的防治提供新的干预手段。

Cardiac ischemia reperfusion injury (MIRI) is an unavoidable pathological damage during the treatment of ischemic heart disease. It is also the main reason that restricts the clinical coronary recanalization effect and leads to postoperative heart failure. There is a lack of effective medicine prevention and treatment methods. EDP3 is a novel bioactive peptide found from the secretion components of ischemic preconditioning endothelial cells and is encoded by LncRNA lnc-ZBTB16-1:1. No functional report has been seen yet. Preliminary experiments have found that EDP3 has the function of preventing from MIRI and reducing myocardial oxidative injury; transcriptome sequencing combined with western blot verification found that the Nrf2 pathway is the key to EDP3 biological function; Nrf2 is known to regulate redox balance and prevent MIRI. This subject intends to further comprehensively demonstrate the prevention and treatment effects of EDP3 on MIRI at the different cells and animal models; and rescue experiments will be carried out to explore the coding gene, underlying molecular mechanisms and the direct target of EDP3. The study is expected to provide novel intervention in MIRI prevention and treatment in future.