缺血性室性心律失常是导致冠心病患者猝死的主要因素。已知多种离子通道表达和功能异常（包括钠通道Nav1.5和钾通道Kv7.1）参与了缺血性室性心律失常发生，但其具体机制仍不清楚。前期我们报道类泛素蛋白FAT10具有促进蛋白稳定性的作用，缺氧可以同时增加心肌细胞FAT10、Nav1.5 和Kv7.1表达。由此我们推测FAT10可能通过上调Nav1.5和Kv7.1介导缺血性室性心律失常。为了验证这一假设，本课题将应用FAT10基因敲除和转基因小鼠等多种实验手段，确认FAT10 在缺血性室性心律失常中作用；解析FAT10稳定Nav1.5和Kv7.1蛋白表达的分子机制，探索阻滞FAT10并联合传统抗心律失常药物的有效治疗作用。最终我们将阐明FAT10介导室性心律失常的详细机制，并有可能找到治疗缺血性室性心律失常多通道阻滞作用的潜在药物靶点。

The lethal ischemic ventricular arrhythmias are the major cause of sudden cardiac death in patients with coronary heart disease. It has been known that the alternation of the expression and function in several cardiac ionic channels (i.e. Nav1.5 and Kv7.1) is associated with lethal ischemic ventricular arrhythmias while the pathogenic mechanism is unclear, and no effective medicine is available. Our previous study firslty explored that ubiquitin-like protein FAT10 could improve the protein stabilization in heart . Besides, we also demonstrated that the expression level of FAT10, Nav1.5 and Kv7.1 were increased in hypoxic cardiomyocytes. Accordingly, we speculate that the up-regulation of Nav1.5 and Kv7.1 by FAT10 might be involved in ischemia-induced ventricular arrhythmias. Expressional and functional studies will be evaulated in myocytes from the FAT10 knock-out mice, transgenic mice, and null mice by multiple experimental techniques to confirm the role of FAT10, Nav1.5 and Kv7.1 in the ischemic ventricular arrhythmias, to explore the stabilization mechanism of Nav1.5 and Kv7.1 by FAT10 and study the effective treatment of FAT10 inhibiting with traditional anti-arrhythmic drugs. Finally, the detailed mechanisms of ventricular arrhythmias mediated by FAT10 would be clarified and the potential anti-ischemia arrhythmic drug target could be found.