Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. The relationship between PSMB4 and cardiomyocyte apoptosis during myocardial I/R is unknown. In this study, PSMB4 expression increased in rat myocardial I/R model, positively correlated with cleaved caspase-3 expression, negatively correlated with Bcl-2 expression. In vitro, neonatal ventricle cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed to mimic myocardial I/R. PSMB4 silence promoted cardiomyocyte apoptosis and IκBα expression, inhibited the activation of NF-κB. On the contrary, PSMB4 overexpession inhibited cardiomyocyte apoptosis and IκBα expression, promoted the activation of NF-κB. Additionally, PSMB4-IκBα interaction was identified, suggesting that PSMB4 might participate in the proteasome dependent degradation of IκBα. The data indicates that PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial I/R, which can supply novel molecular target for the treatment of ischemic heart disease.

心肌缺血/再灌注 (I/R) 损伤诱导心肌细胞凋亡使心脏功能恶化。因此，如何抑制心肌细胞凋亡是近期研究的重点。蛋白酶体家族成员 PSMB4（蛋白酶体亚基 beta 4 型）促进细胞存活。心肌 I/R 期间 PSMB4 与心肌细胞凋亡之间的关系尚不清楚。本研究中，大鼠心肌 I/R 模型中 PSMB4 表达增加，与 cleaved caspase-3 表达呈正相关，与 Bcl-2 表达呈负相关。在体外，构建了新生儿心室心肌细胞缺氧/复氧（H/R）模型以模拟心肌I/R。PSMB4沉默促进心肌细胞凋亡和IκBα表达，抑制NF-κB活化。相反，PSMB4 过度表达抑制心肌细胞凋亡和 IκBα 表达，促进 NF-κB 的活化。此外，鉴定了 PSMB4-IκBα 相互作用，表明 PSMB4 可能参与 IκBα 的蛋白酶体依赖性降解。数据表明，PSMB4通过激活心肌I/R过程中的NF-κB信号通路抑制心肌细胞凋亡，可为缺血性心脏病的治疗提供新的分子靶点。