去乙酰化酶家族综述：肾纤维化的关键调节因子和新兴治疗靶点
A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.
摘要(中文译文)
肾纤维化是慢性肾脏病（CKD）进展的共同病理终点，然而有效的治疗手段仍然有限。Sirtuins家族（SIRT1-SIRT7）作为NAD依赖性去乙酰化酶，是连接代谢、应激反应和稳态的关键分子枢纽。本综述系统阐述了sirtuins整合性的抗纤维化机制：SIRT1、SIRT3和SIRT6抑制TGF-β/Smad和Wnt/β-catenin信号通路；激活AMPK/PGC-1α轴以纠正代谢紊乱；通过FoxO和TFEB促进自噬；并通过Nrf2和NF-κB调控减轻氧化应激和炎症。我们进一步总结了多种靶向sirtuins的治疗策略——包括天然化合物、中药复方、合成药物、基因治疗、生物活性肽和运动训练——这些策略在临床前模型中展现出显著的抗纤维化疗效。尽管证据令人鼓舞，但临床转化仍面临诸多挑战，包括细胞类型特异性的功能双重性、疾病阶段依赖性效应，以及需要具有更高生物利用度和肾脏靶向性的高选择性调节剂。本综述强调sirtuins作为一个多维调控网络和肾纤维化治疗中极具前景的前沿靶点，同时概述了临床应用的关键障碍和未来方向。
Abstract
Renal fibrosis represents the common pathological endpoint of chronic kidney disease (CKD) progression, yet effective therapies remain limited. The sirtuins family (SIRT1-SIRT7), NAD-dependent deacetylases, functions as a critical molecular hub linking metabolism, stress responses, and homeostasis. This review systematically delineates the integrated anti-fibrotic mechanisms of sirtuins: SIRT1, SIRT3, and SIRT6 suppress TGF-β/Smad and Wnt/β-catenin signaling; activate the AMPK/PGC-1α axis to correct metabolic dysregulation; promote autophagy FoxO and TFEB; and alleviate oxidative stress and inflammation through Nrf2 and NF-κB modulation. We further summarize diverse therapeutic strategies targeting sirtuins-including natural compounds, traditional Chinese medicine formulations, synthetic drugs, gene therapy, bioactive peptides, and exercise training-that exhibit significant anti-fibrotic efficacy in preclinical models. Despite promising evidence, clinical translation faces challenges including cell-type-specific functional duality, disease-stage-dependent effects, and the need for highly selective modulators with improved bioavailability and renal targeting. This review highlights sirtuins as a multi-dimensional regulatory network and a promising therapeutic frontier in renal fibrosis, while outlining key obstacles and future directions for clinical application.
如何引用
AMA
Qiqi Deng, Chaonian Li, Jing Luo, Mengting Yin, Shilei Qian, Li Li. A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.. Renal failure. 2026; doi:10.1080/0886022X.2026.2667561.
APA
Qiqi Deng, Chaonian Li, Jing Luo, Mengting Yin, Shilei Qian, Li Li (2026). A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.. Renal failure. https://doi.org/10.1080/0886022X.2026.2667561
GB/T 7714
Qiqi Deng, Chaonian Li, Jing Luo, Mengting Yin, Shilei Qian, Li Li. A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.[J]. Renal failure, 2026 doi:10.1080/0886022X.2026.2667561.
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