心源性猝死（SCD）是临床急性心肌梗死患者死亡的主要原因。然而，其发生机制尚不完全明确且临床治疗中缺乏预防SCD的有效药物和策略。急性心肌梗死后恶性室性心律失常是SCD触发的决定性因素。本项目组经前期对先导物的合成和筛选，首次发现一种新型人重组蛋白rhbFGF21能够有效维持心肌细胞钙稳态，抑制急性心肌梗死后恶性室性心律失常及SCD的发生。基于前期研究结果及m6A差异基因表达谱分析，提出假设：rhbFGF21可能通过抑制METTL14介导的SERCA2a m6A甲基化修饰，参与维持心肌细胞钙稳态，从而预防SCD的发生。本课题拟利用分子生物学技术、基因敲减技术、电生理等技术，探究rhbFGF21对METTL14介导的SERCA2a m6A修饰作用；阐明rhbFGF21参与维持心肌细胞钙稳态分子机制。为临床相关疾病的治疗开辟新思路，为以FGF21为主要活性成分的新药研发提供充分的理论依据。

Sudden cardiac death (SCD) is the leading cause of death in clinical patients with acute myocardial infarction. However, the mechanism of SCD is not fully understood and there is a lack of effective drugs and strategies to prevent SCD in clinical treatment. Malignant ventricular arrhythmia in the post of acute myocardial infarction is the decisive factor for SCD triggering. After the preliminary synthesis and screening of lead compounds, the project team found a novel recombinant human protein-rhbFGF21could effectively maintain the calcium homeostasis of cardiomyocytes and inhibit the occurrence of malignant ventricular arrhythmia and SCD. Based on the preliminary results and m6A differential gene expression profile analysis, we speculated that rhbFGF21 mainly maintained the calcium homeostasis of cardiomyocytes and prevented SCD by inhibiting METTL14-mediated m6A methylation modification of SERCA2a . Molecular biology technology, gene knockout technology, electrophysiology and other technologies were intended to explore the role of rhbFGF21 on SERCA2a m6A modification mediated by METTL14. To elucidate the molecular mechanism of rhbFGF21 involved in maintaining calcium homeostasis in cardiomyocytes. At the same time, it will open up new ideas for the treatment of related diseases and provide sufficient theoretical basis for the research and development of new drugs with FGF21 as the main active ingredient.