Kv1.5是重要的房颤治疗靶点，临床上高醛固酮血症患者的房颤发病风险增加，醛固酮干预可增加心房Kv1.5通道的表达，但调控机制未明。我们报道NOX/ROS系统与房颤的发生密切相关。预实验显示醛固酮可上调心房肌NOX2、NOX4、ROS及Kv1.5的表达，并增强Kv1.5负载的IKur电流。抗氧化剂及AT1R阻断剂可抑制醛固酮介导的IKur增强。以上结果提示醛固酮/MR可通过激活NOX/ROS系统而上调Kv1.5进而促进房颤发生，同时醛固酮/MR可能与AngII/ AT1R交互作用，共同调控Kv1.5。醛固酮干预2小时及24小时后Kv1.5的表达分别达到峰值，提示醛固酮对Kv1.5调控可能涉及非基因组途径及基因组途径；本项目通过培养心房肌细胞及建立家兔房颤模型，深入探讨醛固酮/MR通过影响NOX/ROS-Kv1.5/IKur，进而影响房颤易感性的分子机制，为MR受体阻断剂治疗房颤提供新证据。

Kv1.5 potassium channel is an important therapeutic target of atrial fibrillation. Patients with hyperaldosteronemia have higher risk of atrial fibrillation than normal people. Our study showed that aldosterone could upregulate Kv1.5 expression by activating mineralocorticoid receptor (MR), but the underlying mechanism remains unknown. Our previous investigation indicated that NADPH oxidase (NOX)/reactive oxygen species (ROS) axis was closely related to the onset of atrial fibrillation. Our recent study showed that aldosterone increased the expression of NOX2, NOX4, Kv1.5, the production of reactive oxygen species and the intensity of IKur current and that antioxidants and Ang II type I receptor (AT1R) antagonists inhibited aldosterone-induced IKur augmentation. The above findings suggest that MR activation may initiate atrial fibrillation by upregulating Kv1.5 expression through activating NOX/ROS axis and that aldosterone/MR signaling may have crosstalk with Ang II/AT1R signaling in the regulation of Kv1.5 expression. In addition, we found that the expression of Kv1.5 peaked at 2 h and 24 h after aldosterone treatment, suggesting that there exist non-genomic and genomic pathway in aldosterone-induced Kv1.5 expression. The present study aims at clarifying how aldosterone/MR regulates Kv1.5/IKur and influences the onset of atrial fibrillation by modulating NOX/ROS axis. The elucidation of the mechanism underlying aldosterone-related Kv1.5/IKur regulation may provide new evidence for the utilization of MR antagonists in the treatment of atrial fibrillation in clinical practice.