Despite advancements in management of acute myocardial infarction, this disease remains one of the leading causes of death. Timely reestablishment of epicardial coronary blood flow is the cornerstone of therapy; however, substantial amount of damage can occur as a consequence of cardiac ischaemia/reperfusion (I/R) injury. It has been previously proposed that the pathway leading to major cell death, apoptosis, is responsible for cardiac I/R injury. Nevertheless, there is compelling evidence to suggest that necroptosis, a programmed necrosis, contributes remarkably to both myocardial injury and microcirculatory dysfunction following cardiac I/R injury. Receptor‐interacting protein kinase 1 (RIPK1), RIPK3, and mixed‐lineage kinase domain‐like pseudokinase (MLKL) are shown as the major mediators of necroptosis. In addition to the traditional perception that RIPK1/RIPK3/MLKL‐dependent plasma membrane rupture is fundamental to this process, several RIPK3‐related pathways such as endoplasmic reticulum stress and mitochondrial fragmentation have also been implicated in cardiac I/R injury. In this review, reports from both in vitro and in vivo studies regarding the roles of necroptosis and RIPK3‐regulated necrosis in cardiac I/R injury have been collectively summarized and discussed. Furthermore, reports on potential interventions targeting these processes to attenuate cardiac I/R insults to the heart have been presented in this review. Future investigations adding to the knowledge obtained from these previous studies are needed in the pursuit of discovering the most effective pharmacological agent to improve cardiac I/R outcomes.

中文翻译：

---

RIPK3 调节的细胞死亡途径和坏死性凋亡在心脏缺血再灌注损伤发病机制中的作用。

尽管急性心肌梗死的治疗取得了进展，但这种疾病仍然是导致死亡的主要原因之一。及时重建心外膜冠状动脉血流是治疗的基石；然而，心脏缺血/再灌注 (I/R) 损伤可能会导致大量损伤。先前已经提出，导致主要细胞死亡、细胞凋亡的途径是造成心脏 I/R 损伤的原因。然而，有令人信服的证据表明程序性坏死，程序性坏死，显着导致心脏 I/R 损伤后的心肌损伤和微循环功能障碍。受体相互作用蛋白激酶 1 (RIPK1)、RIPK3 和混合谱系激酶域样假激酶 (MLK​​L) 被证明是坏死性凋亡的主要介质。除了 RIPK1/RIPK3/MLKL 依赖性质膜破裂是该过程的基础的传统看法外，一些 RIPK3 相关通路如内质网应激和线粒体断裂也与心脏 I/R 损伤有关。在这篇综述中，关于坏死性凋亡和 RIPK3 调节的坏死在心脏 I/R 损伤中的作用的体外和体内研究报告进行了集体总结和讨论。此外，本综述还介绍了针对这些过程以减轻心脏 I/R 损伤的潜在干预措施的报告。在寻求发现最有效的药物以改善心脏 I/R 结果的过程中，需要进一步研究增加从这些先前研究中获得的知识。