呼欣怡, 沈佳妍, 应天昊, 韩玉晓, 张琪, 范冰冰, 王涛, 刘梦扬. 线粒体动力学调控在脂肪性肝病中的作用及机制研究进展J. 药学学报, 2025, 60(8): 2405-2416. DOI: 10.16438/j.0513-4870.2025-0086
引用本文: 呼欣怡, 沈佳妍, 应天昊, 韩玉晓, 张琪, 范冰冰, 王涛, 刘梦扬. 线粒体动力学调控在脂肪性肝病中的作用及机制研究进展J. 药学学报, 2025, 60(8): 2405-2416. DOI: 10.16438/j.0513-4870.2025-0086
HU Xin-yi, SHEN Jia-yan, YING Tian-hao, HAN Yu-xiao, ZHANG Qi, FAN Bing-bing, WANG Tao, LIU Meng-yang. Research progress on the role and mechanism of mitochondrial dynamics regulation in steatotic liver diseaseJ. Acta Pharmaceutica Sinica, 2025, 60(8): 2405-2416. DOI: 10.16438/j.0513-4870.2025-0086
Citation: HU Xin-yi, SHEN Jia-yan, YING Tian-hao, HAN Yu-xiao, ZHANG Qi, FAN Bing-bing, WANG Tao, LIU Meng-yang. Research progress on the role and mechanism of mitochondrial dynamics regulation in steatotic liver diseaseJ. Acta Pharmaceutica Sinica, 2025, 60(8): 2405-2416. DOI: 10.16438/j.0513-4870.2025-0086

线粒体动力学调控在脂肪性肝病中的作用及机制研究进展

Research progress on the role and mechanism of mitochondrial dynamics regulation in steatotic liver disease

  • 摘要: 脂肪性肝病(steatotic liver disease, SLD) 是以肝细胞脂质异常积聚为特征的疾病, 主要分为代谢功能障碍相关脂肪性肝病、酒精相关性肝病和代谢与酒精相关脂肪性肝病。多数患者起初为单纯性脂肪肝, 随着病情进展, 逐渐发展为肝炎、肝纤维化和肝硬化。线粒体是高度动态的细胞器, 通过不断地分裂和融合改变线粒体的形态、大小及位置, 此过程被称为线粒体动力学。线粒体动力学失衡会引发线粒体功能障碍, 导致肝脏细胞脂质沉积增多, 同时肝脏细胞的抗氧化防御能力降低, 活性氧积累引发脂质过氧化, 从而造成脂毒性增加和肝损伤。因此, 在脂肪性肝病的进程中, 线粒体动力学扮演重要的角色。本文以线粒体动力学与线粒体自噬、线粒体内质网结构偶联、线粒体依赖性细胞凋亡的关系为切入点, 系统梳理了目前天然化合物通过调控线粒体动力学相关细胞功能改善脂肪性肝病的作用及机制, 以期为天然化合物治疗脂肪性肝病的后续研究及进一步临床开发与应用提供依据和线索。

     

    Abstract: Steatotic liver disease (SLD) is a disease characterized by abnormal accumulation of lipids in hepatocytes, which includes metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and metabolic dysfunction and alcohol-related liver disease. Most patients only have simple liver steatosis at an early stage, which will gradually develop into hepatitis, liver fibrosis, and cirrhosis as the progression of the disease. Mitochondria is a highly dynamic organelle, which changes its morphology, size, and location by continuous division and fusion. This process is known as mitochondrial dynamics. The imbalanced mitochondrial dynamics can cause the dysfunction of mitochondria, leading to increased lipid deposition in liver cells, as well as antioxidant capacity deficient associated reactive oxygen species accumulation and lipid peroxidation, resulting in increased lipotoxicity and liver injury. Therefore, mitochondrial dynamics play an important role in the development of steatotic liver disease. In this review, the relationship between mitochondrial dynamics and mitophagy, mitochondrial-associated endoplasmic reticulum membranes, and mitochondrial-dependent apoptosis in steatotic liver disease were discussed. In addition, the mechanism role of natural compounds in improving steatotic liver disease via regulating mitochondrial dynamics-related cell functions was also systematically reviewed, aiming to provide the basis and clues for the subsequent investigations and further clinical development and application of natural compounds in the treatment of steatotic liver disease.

     

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