巨噬细胞移动抑制因子对心房肌细胞T型钙电流的调控研究

项目名称： 巨噬细胞移动抑制因子对心房肌细胞T型钙电流的调控研究

项目编号： No.81000084

项目类型： 青年科学基金项目

立项/批准年度： 2011

项目学科： 轻工业、手工业

项目作者： 饶芳

作者单位： 广东省心血管病研究所

项目金额： 10万元

中文摘要： 房颤药物干预副作用大，有效性低，而导管治疗复发率高。目前认为炎症在房颤发病机制中起重要作用。ICa,L的下调和有效不应期的缩短是房颤电重塑的主要因素。我们课题组之前的研究发现前炎症因子MIF可通过调控ICa,L参与房颤的电重塑。但基础和临床研究均证实LCC阻断剂治疗房颤的效果不佳，而TCC阻断剂明显优于LCC阻断剂。因此本项目研究人体中MIF是否与TCC的表达相关；体外细胞模型观察MIF是否参与心房肌细胞ICa,T的调控，是通过直接影响通道功能，还是影响TCC的基因和/或蛋白表达来实现；进一步观察Src激酶是否参与ICa,T的调控，以及MIF对ICa,T的调控是否是通过激活Src激酶；并研究心房肌细胞中MIF的上游调控途径，以及相关的激酶信号途径；本项目的研究成果将为进一步阐明房颤的发病机制提供理论依据和实验基础，为临床上房颤的治疗提供新的靶点。

中文关键词： 心房纤颤；巨噬细胞移动抑制因子；T型钙通道；蛋白激酶

英文摘要： Atrial fibrillation (AF) is the most frequently encountered arrhythmia in clinical practice and is associated with significant morbidity, mortality and healthcare cost. However, its prevention and treatment are very difficult and remain a major challenge, therefore achieving a better understanding of the pathogenesis of AF is very important. Down-regulation of L-type Ca2+ channel current (ICa,L) and the shortening of effective refractory period are the key factor in electrical remodeling of AF. In our previous study, we have tested that whether reduced ICa,L amplitude in AF is associated with increased MIF levels. But basic and clinical research have indicated that in the long term tachycardia-induced atrial remodeling of dogs, the TCC blockers proved more effective than the selective L-type blockers. Therefore, in the present study, we investigated whether and how MIF regulates ICa,T, how to response to the renin-angiotensin system (RAS) and oxidative stress and the role of Src kinase in atiral myocytes;

英文关键词： Macrophage migration inhibitory factor; HL-1 cells; T-type Ca2+ channel; Atrial fibrillation; Protein kinases