Mitochondrial damage is involved in the pathogenesis of post-infarction cardiac injury. However, the upstream regulators of mitochondrial damage have not yet been identified. The aim of our study is to explore the role of Sirt3 in post-infarction cardiac injury with a particular focus on mitochondrial fission and AMPK-Drp1 pathways. Our results indicated that Sirt3 was downregulated in the progression of post-infarction cardiac injury. Overexpression of Sirt3 attenuated cardiac fibrosis, sustained myocardial function, inhibited the inflammatory response, and reduced cardiomyocyte death. Functional studies illustrated that chronic post-infarction cardiac injury was characterized by increased mitochondrial fission, which triggered mitochondrial oxidative stress, metabolic disorders, mitochondrial potential reduction and caspase-9 apoptosis in cardiomyocytes. However, Sirt3 overexpression attenuated mitochondrial fission and thus preserved mitochondrial homeostasis and cardiomyocyte viability. Furthermore, our results confirmed that Sirt3 repressed mitochondrial fission via normalizing AMPK-Drp1 pathways. Inhibition of AMPK activity re-activated Drp1 and thus abrogated the inhibitory effect of Sirt3 on mitochondrial fission. Altogether, our results indicate that Sirt3 enhancement could be an effective approach to retard the development of post-infarction cardiac injury via disrupting mitochondrial fission and normalizing the AMPK-Drp1 axis.

中文翻译：

---

Sirt3通过抑制线粒体裂变和AMPK-Drp1通路的正常化来减轻梗塞后心脏的损伤。

线粒体损伤与梗死后心脏损伤的发病机理有关。但是，尚未发现线粒体损伤的上游调节剂。我们研究的目的是探讨Sirt3在梗死后心脏损伤中的作用，特别关注线粒体裂变和AMPK-Drp1途径。我们的结果表明，Sirt3在梗死后心脏损伤的进展中被下调。Sirt3的过表达减弱了心脏纤维化，持续的心肌功能，抑制了炎症反应并减少了心肌细胞的死亡。功能研究表明，慢性梗死后心脏损伤的特征在于线粒体裂变增加，从而触发线粒体氧化应激，代谢紊乱，心肌细胞线粒体电位降低和caspase-9凋亡 但是，Sirt3的过表达减弱了线粒体的裂变，从而保持了线粒体的稳态和心肌细胞的生存能力。此外，我们的结果证实Sirt3通过使AMPK-Drp1通路正常化来抑制线粒体裂变。AMPK活性的抑制重新激活Drp1，从而废除了Sirt3对线粒体裂变的抑制作用。总之，我们的结果表明，Sirt3增强可能是通过破坏线粒体裂变并使AMPK-Drp1轴正常化来延迟梗塞后心脏损伤发展的有效方法。我们的结果证实，Sirt3通过使AMPK-Drp1通路正常化来抑制线粒体裂变。AMPK活性的抑制重新激活Drp1，从而废除了Sirt3对线粒体裂变的抑制作用。总之，我们的结果表明，Sirt3增强可能是通过破坏线粒体裂变并使AMPK-Drp1轴正常化来延迟梗塞后心脏损伤发展的有效方法。我们的结果证实，Sirt3通过使AMPK-Drp1通路正常化来抑制线粒体裂变。AMPK活性的抑制重新激活Drp1，从而废除了Sirt3对线粒体裂变的抑制作用。总之，我们的结果表明，Sirt3增强可能是通过破坏线粒体裂变并使AMPK-Drp1轴正常化来延迟梗塞后心脏损伤发展的有效方法。