Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Department of Nephrology, 980th Hospital of PLA Joint Logistical Support Force (Bethune International Peace Hospital), Shijiazhuang, 050011, China.
QJM. 2024 Apr 12;117(4):247-255. doi: 10.1093/qjmed/hcad152.
Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.
急性肾损伤（AKI）是一种预后不良的复杂临床综合征，增加了慢性肾脏病和终末期肾病发展的风险。然而，AKI 的潜在机制仍未完全阐明，有效的预防和治疗策略仍然缺乏。由于滤过和吸收需要大量的能量，肾脏富含线粒体，这无疑与 AKI 的发生或进展有关。最近有大量证据表明，Sirtuin 3（SIRT3）是线粒体中表达最显著的去乙酰化酶之一，对 AKI 具有保护作用。SIRT3 通过调节能量代谢、抑制氧化应激、抑制炎症、改善细胞凋亡、抑制早期纤维化和维持线粒体平衡来防止 AKI。此外，一些 SIRT3 激活剂在动物模型和体外实验中均表现出肾脏保护作用，但尚未应用于临床实践，这表明这是一种很有前途的治疗方法。在这篇综述中，我们梳理和总结了 SIRT3 研究的最新进展以及 SIRT3 激活剂在 AKI 中的潜在治疗作用。
