Mitochondrial abnormality and oxidative stress in nonalcoholic steatohepatitis
Mitochondrial abnormality and oxidative stress in nonalcoholic steatohepatitis
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DOI：
10.1111/j.1530-0277.2006.00288.x
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Tamagawa, Yasuhiro
中科院分区：
文献类型：
--
作者：
Kojima, Hideyuki;Sakurai, Shinya;Tamagawa, Yasuhiro
背景：氧化应激在非酒精性脂肪性肝炎（NASH）的发病机制中起主要作用。线粒体异常可能通过线粒体活性氧的过度形成与NASH的发生和进展相关。本研究旨在探讨线粒体异常在NASH中的作用及其与氧化应激的关系。方法：对26例NASH患者、11例单纯脂肪变性患者和10例健康志愿者进行临床病理分析。肝/脾比，肝脂肪含量的指数，用计算机断层扫描进行了评价。血浆谷胱甘肽水平作为抗氧化标记物，尿8-异前列腺素水平和肝脏中的3-硝基酪氨酸染色作为氧化应激标记物。线粒体异常通过血清线粒体天冬氨酸转氨酶（mAST）水平和肝脏线粒体染色来估计。结果：NASH患者尿8-异前列腺素水平高于健康志愿者，而血浆谷胱甘肽水平在2组中相似。在NASH中，尿8-异前列腺素水平与丙氨酸转氨酶水平呈正相关，与肝/脾比值呈负相关。3-硝基酪氨酸染色在单纯性脂肪变性和NASH中比在正常肝脏中更高级，但在单纯性脂肪变性和NASH中相似。与健康志愿者和单纯性脂肪变性的正常mAST水平相比，四分之一的NASH患者的血清mAST水平升高，并且与NASH患者的尿8-异前列烷水平呈正相关。大多数NASH病例表现为弥漫性或局灶性，但强烈的线粒体染色在肝脏中的散在染色在简单的脂肪ates.Conclusions：我们目前的研究表明，在NASH，增强氧化应激可能与肝脏炎症和脂肪浸润的程度在肝脏。然而，单纯性脂肪变性和NASH均暴露于氧化应激，而NASH单独与线粒体异常相关。这些结果表明，线粒体异常可能在NASH的发生和发展中发挥作用，与氧化应激相关。
Background: Oxidative stress plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Mitochondrial abnormality may be associated with the onset and progression of NASH via excessive formation of mitochondrial reactive oxygen species. This study aimed to investigate the role of mitochondrial abnormality in NASH in relation to oxidative stress.Methods: Twenty-six patients with NASH, 11 with simple steatosis, and 10 healthy volunteers underwent clinico-pathological analysis. The liver/spleen ratio, an index of the hepatic fat content, was evaluated with computed tomography. Plasma glutathione levels were measured as an antioxidative marker, and the urinary 8-isoprostane levels and 3-nitrotyrosine staining in the liver as an oxidative stress marker. Mitochondrial abnormality was estimated by serum levels of mitochondria aspartate transaminase (mAST) and the mitochondrial staining in the liver.Results: Urinary 8-isoprostane levels were higher in NASH than in the healthy volunteers, whereas plasma glutathione levels were similar in the 2 groups. In NASH, urinary 8-isoprostane levels positively correlated with alanine transaminase levels and negatively with the liver/spleen ratio. The 3-nitrotyrosine staining was more advanced in simple steatosis and NASH than in the normal liver, but was similar in simple steatosis and NASH. In contrast to the normal mAST levels in the healthy volunteers and simple steatosis, serum mAST levels were elevated in one-fourth of the NASH patients and positively correlated with urinary 8-isoprostane levels in NASH. Most cases of NASH showed diffuse or focal but intense mitochondrial staining in the liver in contrast to scattered staining in simple steatosis.Conclusions: Our present study demonstrated that in NASH, the enhanced oxidative stress may be associated with hepatic inflammation and the degree of fat infiltration in the liver. However, simple steatosis and NASH were both exposed to oxidative stress, while NASH alone was associated with mitochondrial abnormality. These findings indicate that mitochondrial abnormality may play a role in the onset and progression of NASH in correlation with oxidative stress.