Ischemia-reperfusion (I/R) injury occurs during cardiac surgery and is the major factor leading to heart dysfunction and heart failure. Our previous study showed that gene and microRNA expression profiles are altered in heart grafts with extended I/R injury. In this study, we, for the first time, demonstrated that I/R injury upregulates the expression of Polo-like kinase 2 (Plk2) but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using small interfering RNA (siRNA) protects cells from Antimycin A-induced cell apoptosis/death. Silencing Plk2 also decreases phosphorylated p65 expression but increases Angiopoietin 1 expression. In addition, Plk2 is negatively regulated by miR-128. miR-128 exerts a protective effect on cell apoptosis similar to Plk2 siRNA in response to I/R stress. Methylation inhibitor 5-azacytidine (5-AZ) increases the expression of miR-128 and subsequently reduces Plk2 expression and cell apoptosis. In conclusion, this study demonstrated that Plk2 regulated by miR-128 induces cell apoptosis/death in response to I/R stress through activation of the nuclear factor κB (NF-κB) signal pathway. miR-128 and Plk2 are new targets for preventing cardiac I/R injury or oxidative stress-mediated injury.

缺血再灌注（I / R）损伤发生在心脏手术期间，是导致心脏功能障碍和心力衰竭的主要因素。我们先前的研究表明，具有延长的I / R损伤的心脏移植物中的基因和microRNA表达谱发生了改变。在这项研究中，我们首次证明I / R损伤在体外和体内均可上调Polo样激酶2（Plk2）的表达，但会降低心脏细胞中miR-128的表达。。使用小干扰RNA（siRNA）沉默Plk2可保护细胞免受抗霉素A诱导的细胞凋亡/死亡的影响。沉默Plk2还降低了磷酸化的p65表达，但增加了血管生成素1的表达。此外，Plk2受到miR-128的负调控。miR-128对细胞凋亡的保护作用类似于对I / R应激的Plk2 siRNA。甲基化抑制剂5-氮杂胞苷（5-AZ）增加miR-128的表达，并随后降低Plk2的表达和细胞凋亡。总之，这项研究表明，miR-128调节的Plk2通过激活核因子κB（NF-κB）信号通路，响应I / R应激诱导细胞凋亡/死亡。miR-128和Plk2是预防心脏I / R损伤或氧化应激介导的损伤的新靶标。