心房颤动（房颤）患病率随年龄增长而增加，增龄是房颤的独立危险因素。本课题组前期的研究表明，增龄引起的心房电生理改变和L-型钙电流密度降低是增龄性房颤发生和维持的重要机制，且增龄性房颤存在心肌纤维化和细胞凋亡的组织形态改变，但这一改变参与增龄性房颤的确切机制尚未阐明。已知MCP-1可促进心肌纤维化，MCPIP参与心肌细胞凋亡。本研究拟通过增龄性房颤犬模型的体内试验和体外细胞培养，利用心电生理、膜片钳、流式细胞术、细胞与分子生物学等技术，观察各组犬MCP-1和MCPIP表达、心房电生理改变、离子通道电流、心房纤维化程度、细胞凋亡等的差异，揭示MCP-1和MCPIP与增龄性房颤、心房纤维化、心房细胞凋亡间的关系，阐明MCP-1和MCPIP诱导的心房纤维化和心肌细胞凋亡参与增龄性房颤心房电重构、离子通道重构发生发展的病理机制，为增龄性房颤的心房重构机制和治疗提供新的思路和理论依据。

The prevalence rate of atrial fibrillation(AF) generally increases with age, thus aging is an independent risk factor of AF. It has already been demonstrated in our previous studies that aging causes atrial physiological changes and decrease the density of L - type calcium current which is known as the important mechanism of occurrence and maintenance of age-related AF. Furthermore , histological changes of myocardial fibrosis and apoptosis are found in age-related AF, but the exact mechanism still remains unclear. It has been shown that monocyte chemoattractant protein-1(MCP-1) promotes the myocardial fibrosis, monocyte chemotactic protein-1 induced protein (MCPIP) is involved in myocardial apoptosis. In this study, an experimental in vivo canine model with age-related AF and in vitro cell culture will be performed, by using the technical approaches such as cardiac electrophysiology, patch clamp, flow cytometry, cellular and molecular biology. We will observe the difference in the expression of MCP-1 and MCPIP, atrial electrophysiological changes, ion channel currents, extent of atrial fibrosis and cellular apoptosis in different canine group. We aim to reveal the relationship between MCP-1, MCPIP and the occurrence of age-related AF, atrial fibrosis , atrial cellular apoptosis, to illustrate the pathological mechanism which atrial fibrosis and myocardial apoptosis induced by MCP-1 as well as MCPIP are involved in atrial remodeling and ion channel remodeling in age-related AF. All mentioned above will bring new ideas and will provide the theoretical foundation for the mechanism of atrial remodeling in age-related AF and also for the therapy.