心房颤动（房颤）临床常见，是一种从阵发到持续再到慢性逐渐进展的疾病，发生机制包括触发和折返，复杂的电与结构重塑贯穿于这个进展过程。多个离子通道的上调或下调参与房颤的电重塑，心房肌纤维化过程主要参与结构重塑。离体心脏模型的研究发现晚钠电流增大诱发的房颤建立在动作电位时程延长及钙相关途径激活的基础上。我们采用绵羊心房不连续快速起搏诱发房颤从阵发到持续进展过程的慢性动物模型证明：房颤发生时心房肌细胞的晚钠电流增大，自噬明显增加，采用RAAS阻滞剂可减轻结构重塑，但对房颤本身无抑制作用。本研究从晚钠电流激活途径参与的电重塑和自噬/纤维化参与的结构重塑出发，在慢性房颤模型上从分子、细胞和整体动物水平进行研究，并使用选择性晚钠电流抑制剂干预电重塑的过程，可以明确晚钠电流-CaMK-细胞内钙通路相关的电重塑和以自噬/纤维化为特征的结构重塑在房颤从阵发到持续进展中的作用及相互关系，为房颤治疗提供新的思路。

Atrial fibrillation (AF) is clinically common with progression from paroxysmal to persistent during a period of time. The mechanisms include triggered activity and re-entry, with complicated electrical and structural remodeling of atria throughout the whole process. Multiple ion channels are either up-regulated or down-regulated during the electrical remodeling, and atrial fibrosis is mainly underlying the structural remodeling. Results from the isolated rabbit heart research indicated that increased late INa induced AF was based on the prolongation of action potential duration and the activation of calcium-related pathways. In this study, we are using a developed intermittent tachypacing-induced AF in a sheep model to find the increase in late sodium current and autophagy of atrial myocytes. Compared to the accomplished research work where RAAS inhibitor reduced substrate remodeling but didn’t affect the progression of AF. We will determine that late sodium current-associated CaMK-calcium pathway is involved in the electrical remodeling of AF and the autophagy-fibrosis involved substrate remodeling in sheep AF model from research at the molecular, cellular and holistic animal levels. Selective late sodium current inhibitor inhibits the process of electrical remodeling. Confirming the effects and relation of late sodium current-CaMK-intracellular calcium pathway-related electrical remodeling and mechanical remodeling characterized by autophagy/fibrosis on the progression from paroxysmal to persistent atrial fibrillation, which may help to develop new therapeutic strategy for AF.