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诱导自噬作为非酒精性脂肪性肝病的治疗突破:当前证据与展望

Induction of Autophagy as a Therapeutic Breakthrough for NAFLD: Current Evidence and Perspectives.

作者信息

Liu Yanke, Zhang Mingkang, Wang Yazhi

机构信息

Department of Laboratory Medicine, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, China.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China.

出版信息

Biology (Basel). 2025 Aug 4;14(8):989. doi: 10.3390/biology14080989.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management.

摘要

非酒精性脂肪性肝病(NAFLD)是一种临床病理综合征,其特征为在无大量饮酒或其他特定肝损伤原因的情况下出现肝脏脂肪变性。它已成为全球肝功能障碍的主要原因之一。然而,NAFLD确切的病理生理机制仍不清楚,有效的治疗策略仍在研究中。自噬是真核细胞中一个重要的细胞内过程,它通过膜运输途径实现细胞质成分的降解和再循环。最近的研究表明,自噬功能受损或缺陷与NAFLD的发生和发展密切相关。恢复自噬功能可能是减轻肝细胞损伤的关键途径。然而,由于自噬调节的复杂性及其对细胞功能的背景依赖性影响,针对NAFLD中自噬的治疗策略仍然有限。本综述旨在总结自噬与NAFLD之间的关系,重点关注自噬这一核心机制。我们讨论了饮食和运动、药物治疗(包括现代药物治疗和植物源化合物)以及其他方法(如激素、纳米颗粒、肠道微生物群和维生素)等干预措施的最新研究进展。此外,我们简要强调了潜在的自噬相关分子靶点,这些靶点可能为NAFLD的管理提供新的治疗思路。

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