Recent studies have shown that several upstream signaling elements of apoptosis and necroptosis are closely associated with acute injury in the heart. In our study, we observed that miR-105 was notably dysregulated in rat hearts with myocardial infarction (MI). Thus, the purpose of this study was to test the hypothesis that miR-105 participates in the regulation of RIP3/p-MLKL- and BNIP3-dependent necroptosis/apoptosis in H9c2 cells and MI rat hearts. Our results show that the RIP3/p-MLKL necroptotic pathway and BNIP3-dependent apoptosis signaling are enhanced in H9c2 cells under hypoxic conditions, whereas, compared with these pathways in the controls, those in miR-105-treated H9c2 cells are suppressed. Mechanistically, we identified miR-105 as the miRNA directly suppressing the expression of RIP3 and BNIP3, two important mediators involved in cell necroptosis and apoptosis. Furthermore, MI rat hearts injected with miR-105 had decreased infarct sizes, indicating that miR-105 is among three miRNAs that function simultaneously to suppress necroptotic/apoptotic cell death pathways and to inhibit MI-induced cardiomyocyte cell death at multiple levels. Taken together, miR-105 may constitute a new therapeutic strategy for cardioprotection in ischemic heart disease.

最近的研究表明，凋亡和坏死性坏死的一些上游信号传导元件与心脏的急性损伤密切相关。在我们的研究中，我们观察到miR-105在患有心肌梗塞（MI）的大鼠心脏中明显失调。因此，本研究的目的是检验miR-105参与H9c2细胞和MI大鼠心脏中RIP3 / p-MLKL-和BNIP3依赖的坏死性/凋亡的调节的假设。我们的结果表明，在低氧条件下，H9c2细胞中RIP3 / p-MLKL坏死性途径和BNIP3依赖性凋亡信号增强，而与对照组中的这些途径相比，miR-105处理的H9c2细胞中的这些途径被抑制。从机理上讲，我们将miR-105鉴定为直接抑制RIP3和BNIP3表达的miRNA，细胞坏死和细胞凋亡的两个重要介体。此外，注射miR-105的MI大鼠心脏的梗死面积减小，表明miR-105是同时发挥抑制坏死性/凋亡性细胞死亡途径并在多个水平上抑制MI诱导的心肌细胞死亡的三种miRNA之一。综上所述，miR-105可能构成缺血性心脏病心脏保护的新治疗策略。