经由线粒体损伤诱发的药源性肝损伤研究进展

Research Progress in Drug-induced Liver Injury via Mitochondrial Damage

线粒体是物质氧化和能量转换的场所,在能量代谢及自由基的产生、衰老、凋亡中起着重要作用。线粒体的呼吸链缺陷、代谢酶失活、结构改变、基因突变等因素都会影响整个细胞的正常功能,从而导致病变的发生。线粒体是药物毒性作用的重要靶标,肝脏作为药物代谢的重要脏器,也是药物引发损伤的主要靶器官。一些抗病毒药物、抗肿瘤药物和抗生素等可显著诱导肝脏线粒体损伤。药物主要通过改变线粒体结构、酶的活性或减少mtDNA的合成,进一步破坏β-脂质氧化和肝细胞的氧化能力,最终诱发肝损伤。综述药源性肝损伤领域有关线粒体损伤的研究进展,为预防和诊断药源性肝损提供思路。

Mitochondria are major organelles of energy generation and material oxidation in cell and play a fundamental role in energy metabolism, free radicals production, aging, and apoptotic regulation.The possible factors leading to mitoehondrial dysfunction include respiratory chain defects, metabolic enzyme inactivation, structural changes, mutations, etc. All of which will affect the normal function of the cells, resulting in the occurance of diseases. M itochondria are important targets of drug toxicity, and the liver is also a major target of drug damage because it is an important organ of drug metabolism. A variety of clinical drugs, such as antivirals, anti-cancer drugs and antibiotics have significantly shown the inducible mitochondrial injury of liver.Drugs induced liver injury primarily by changing the activity of enzyme and the structure of mitochondrial and/or decreasing the synthesis of mtDNA, further underulining β-lipid oxidation and the oxidative of liver cells.This paper provides the overview of research progress on the role of mitochondrial damage in drug-induced liver injury and gives thoughts on the prediction and prevention of drug-induced liver injury.