RNase L is generally thought to play a key role in antiviral defenses. Although RNase L protein and mRNA are known to be highly expressed in myocardial tissue, there are few studies of the potential functions of RNase L in myocardial tissue. In this study, we tested the hypothesis that RNase L may be involved in the pathological process of cardiac ischemic injury. RNase L-overexpressing and RNase L knockdown H9c2 cell lines were subjected to the oxygen and glucose deprivation (OGD) model, and RNase L knockout mice were subjected to acute myocardial infarction surgical procedures to investigate the function of RNase L in ischemic heart injury. OGD induced abnormal aggregation of double-stranded RNA in H9c2 cells, activated RNase L within 6 h of OGD initiation, and mediated apoptosis via the c-Jun N-terminal kinase pathway. In addition, RNase L knockout mice were more tolerant of myocardial infarction, and this knockout protected heart function and prevented pathological ventricular remodeling. Notably, both in in vivo and in vitro experiments, RNase L was gradually diminished during prolonged ischemic injury, which we speculate is an adaptive protective response serving to reduce myocardial ischemic damage. These results suggest that RNase L plays a role in the pathological process of cardiac acute ischemic injury. It is first activated by ischemic injury, causing cardiomyocyte death, but gradually diminishes to protect the heart from further damage.

中文翻译：

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RNase L在心脏急性缺血性损伤中的功能及其降解机制。

通常认为RNase L在抗病毒防御中起关键作用。尽管已知RNase L蛋白和mRNA在心肌组织中高表达，但很少有关于RNase L在心肌组织中潜在功能的研究。在这项研究中，我们检验了RNase L可能参与心脏缺血性损伤的病理过程的假设。将过表达RNase L的细胞和敲除RNase L的H9c2细胞系进行氧和葡萄糖剥夺（OGD）模型，并对RNase L敲除的小鼠进行急性心肌梗死外科手术，以研究RNase L在缺血性心脏损伤中的功能。OGD诱导H9c2细胞中双链RNA异常聚集，在OGD启动后6小时内激活RNase L，并通过c-Jun N端激酶途径介导凋亡。此外，RNase L敲除小鼠对心肌梗塞的耐受性更高，这种敲除可保护心脏功能并防止病理性心室重构。值得注意的是，在体内和体外实验中，RNase L在长时间的缺血性损伤中均逐渐减少，我们推测这是一种适应性保护性反应，可减少心肌缺血性损伤。这些结果表明，RNase L在心脏急性缺血性损伤的病理过程中起作用。它首先被缺血性损伤激活，引起心肌细胞死亡，但逐渐减少以保护心脏免受进一步损害。在长时间的缺血性损伤中，RNase L逐渐减少，我们推测这是一种适应性保护性反应，可减少心肌缺血性损伤。这些结果表明，RNase L在心脏急性缺血性损伤的病理过程中起作用。它首先被缺血性损伤激活，引起心肌细胞死亡，但逐渐减少以保护心脏免受进一步损害。在长时间的缺血性损伤中，RNase L逐渐减少，我们推测这是一种适应性保护性反应，可减少心肌缺血性损伤。这些结果表明，RNase L在心脏急性缺血性损伤的病理过程中起作用。它首先被缺血性损伤激活，引起心肌细胞死亡，但逐渐减少以保护心脏免受进一步损害。