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首页> 外文期刊>European journal of gastroenterology and hepatology >Mitochondrial injury in steatohepatitis.
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Mitochondrial injury in steatohepatitis.

机译：脂肪性肝炎的线粒体损伤。

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Rich diet and lack of exercise are causing a surge in obesity, insulin resistance and steatosis, which can evolve into steatohepatitis. Patients with non-alcoholic steatohepatitis have increased lipid peroxidation, increased tumour necrosis factor-alpha (TNF-alpha) and increased mitochondrial beta-oxidation rates. Their in-vivo ability to re-synthesize ATP after a fructose challenge is decreased, and their hepatic mitochondria exhibit ultrastructural lesions, depletion of mitochondrial DNA and decreased activity of respiratory chain complexes. Although the mechanisms for these effects is unknown, the basal cellular formation of reactive oxygen species (ROS) may oxidize fat deposits to cause lipid peroxidation, which damages mitochondrial DNA, proteins and cardiolipin to partially hamper the flow of electrons within the respiratory chain. This flow may be further decreased by TNF-alpha, which can release cytochrome c from mitochondria. Concomitantly, the increased mitochondrial fatty acid beta-oxidationrate augments the delivery of electrons to the respiratory chain. Due to the imbalance between a high electron input and a restricted outflow, electrons may accumulate within complexes I and III, and react with oxygen to form the superoxide anion radical. Increased mitochondrial ROS formation could in turn directly oxidize mitochondrial DNA, proteins and lipids, enhance lipid peroxidation-related mitochondrial damage, trigger hepatic TNF-alpha formation and deplete antioxidants, thus further blocking electron flow and further increasing mitochondrial ROS formation. Mitochondrial dysfunction plays an important role in liver lesions, through the ROS-induced release of both biologically active lipid peroxidation products and cytokines. In particular, the up-regulation of both TNF-alpha and Fas triggers mitochondrial membrane permeability and apoptosis. The ingestion of apoptotic bodies by stellate cells stimulates fibrogenesis, which is further activated by lipid peroxidation products and high leptin levels. Chronic apoptosis is compensated by increased cell proliferation, which, together with oxidative DNA damage, may cause gene mutations and cancer.
机译：饮食过多和缺乏运动会导致肥胖，胰岛素抵抗和脂肪变性激增，并可能演变为脂肪性肝炎。非酒精性脂肪性肝炎患者的脂质过氧化增加，肿瘤坏死因子-α（TNF-α）增多和线粒体β-氧化率增加。在果糖攻击后，它们体内重新合成ATP的能力降低，并且肝线粒体表现出超微结构损伤，线粒体DNA耗竭和呼吸链复合物活性降低。尽管这些作用的机制尚不清楚，但活性氧（ROS）的基础细胞形成可能会氧化脂肪沉积，从而引起脂质过氧化，从而损害线粒体DNA，蛋白质和心磷脂，从而部分阻碍呼吸链内电子的流动。 TNF-α可以进一步减少这种流动，它可以从线粒体释放细胞色素c。随之而来的是，线粒体脂肪酸β-氧化率的增加增加了电子向呼吸链的传递。由于高电子输入和受限制的流出之间的不平衡，电子可能在配合物I和III中积累，并与氧反应形成超氧阴离子自由基。线粒体ROS形成的增加反过来可以直接氧化线粒体DNA，蛋白质和脂质，增强脂质过氧化相关的线粒体损伤，触发肝TNF-α的形成并耗尽抗氧化剂，从而进一步阻断电子流并进一步增加线粒体ROS的形成。线粒体功能障碍通过ROS诱导的生物活性脂质过氧化产物和细胞因子的释放，在肝损伤中起重要作用。特别是，TNF-α和Fas的上调都会触发线粒体膜通透性和凋亡。星状细胞摄入凋亡小体会刺激纤维化，脂质过氧化产物和瘦素水平高会进一步激活纤维化。慢性细胞凋亡可通过增加细胞增殖来补偿，细胞增殖与氧化性DNA损伤一起可能导致基因突变和癌症。

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