Heart failure (HF) is a major cause of death in cardiovascular diseases worldwide, and its molecular mechanisms and effective prevention strategies remain to be further studied. The myocardial cytoskeleton plays a pivotal role in many heart diseases. However, little is known about the function of the membrane cytoskeleton 4.1 protein family and related regulatory mechanisms in the pathogenesis of HF. In this study, we detected the localization and expression of the protein 4.1 family and ion channel proteins in a rat HF model induced by doxorubicin (DOX), and studied the interactions between them. Our results showed that compared with the control group, the HF group displayed an increased expression level of protein 4.1R and decreased levels of protein 4.1 G and 4.1 N. The Nav1.5 protein levels were significantly increased, while the SERCA2a and Cav1.2 protein levels were significantly decreased in the HF group. Furthermore, there is co-localization and interaction between protein 4.1R and Nav1.5, protein 4.1 G and SERCA2a, protein 4.1 N and Cav1.2, respectively. Taken together, the results indicated that the protein 4.1 family might be involved in the occurrence and development of HF through its interaction with ion channel proteins, suggesting that 4.1 proteins may serve as a novel therapeutic target for HF.

心力衰竭（HF）是全球心血管疾病的主要死因，其分子机制和有效预防策略仍有待进一步研究。心肌细胞骨架在许多心脏病中起关键作用。然而，关于膜细胞骨架 4.1 蛋白家族在 HF 发病机制中的功能和相关调控机制知之甚少。在本研究中，我们检测了多柔比星 (DOX) 诱导的大鼠心衰模型中蛋白 4.1 家族和离子通道蛋白的定位和表达，并研究了它们之间的相互作用。我们的结果表明，与对照组相比，HF组显示出蛋白4.1R的表达水平升高，蛋白4.1 G和4.1 N的水平降低。Nav1.5蛋白水平显着升高，而 HF 组 SERCA2a 和 Cav1.2 蛋白水平显着降低。此外，蛋白质 4.1R 和 Nav1.5、蛋白质 4.1 G 和 SERCA2a、蛋白质 4.1 N 和 Cav1.2 分别存在共定位和相互作用。综上所述，结果表明4.1蛋白家族可能通过与离子通道蛋白的相互作用参与HF的发生和发展，提示4.1蛋白可作为HF的新治疗靶点。