慢性心力衰竭发生心律失常的主要机制是心衰电活动的异常，目前针对心衰合并心律失常并无确切有效地治疗手段。因此，寻找离子通道等电学基质的上游调控靶点可能是未来防治心衰后发生的新思路。S100B蛋白在正常心肌细胞不表达，在心衰心肌细胞表达及分泌却显著升高，与心功能呈负相关。S100B生物学效应主要是通过与RAGE结合来发挥的。RAGE与其配体结合后，激活下游信号通路可上调cx43的表达，增加糖尿病大鼠心律失常的发生，还可促进房颤的发生。然而S100B/RAGE通路对于心衰后室性心律失常及电重构的影响却不明确，尚无国内外报道。本课题通过分别干预S100B及RAGE蛋白功功能，即构建S100B基因敲除和心脏特异性转基因心衰小鼠及给予RAGE抑制剂，探讨S100B/RAGE通路对心衰后室性心律失常及电重构的影响，以明确心衰合并心律失常治疗的最佳靶点，为临床防治心衰后心律失常的发生提供新思路及实验依据。

Chronic heart failure (CHF) is a serious threat to safety and quality of life. Complex ventricular arrhythmias associated with CHF patients, as well as non-sustained ventricular tachycardia higher morbidity, leaded to mortality up to 50 %. Therefore, prevention of arrhythmia after heart failure is critical. Currently arrhythmia research and therapeutic targets focused on ion channels has certain limitations. Therefore, it is essential for the understanding of cardiac electrical activity to find the upstream regulatory targets of ion flow. S100B protein, which has a wide range of biological effects, mediated hypertrophy and apoptosis of myocardial by the receptor of advanced glycation end products (RAGE), and promoted the development of HF. RAGE, a membrane protein, is closely related to cardiovascular disease. Recent researches had shown that the RAGE system upregulated connexin43 expression in rat cardiomyocytes, and promoted the occurrence of atrial fibrillation. From these studies, we infer that S100B/RAGE may play an important role in electrical remodeling after CHF. We will use S100B knockout mice and cardiac-specific S100B transgenic mouse to observe the effects of S100B on electrical remodeling after CHF, and to explore possible mechanisms involved, that is provided new ideas for prevention and treatment of arrhythmia after CHF.