Mitsuyoshi Hironori, Itoh Yoshito, Okanoue Takeshi
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine.
Nihon Rinsho. 2006 Jun;64(6):1077-82.
Oxidative stress plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Reactive oxygen species (ROS) would derive from mitochondria, cytochrome P-450 2E1, peroxisome, and iron overload in the liver with steatosis. These excessive ROS is considered to cause simple steatosis to progress to NASH. On the other hand, oxidative stress exacerbates insulin sensitivity in hepatocytes, while hepatic steatosis causes oxidative stress. Thus, oxidative stress and insulin resistance might be interactive in NASH. Actually, we have found that the grade of steatosis correlates with serum thioredoxin level, a marker of oxidative stress, in NASH patients. Therefore, we propose that the feedback loop of oxidative stress, insulin resistance, and steatosis would play a significant role in the development of NASH.
氧化应激在非酒精性脂肪性肝炎(NASH)的发病机制中起重要作用。活性氧(ROS)可来源于线粒体、细胞色素P-450 2E1、过氧化物酶体以及脂肪变性肝脏中的铁过载。这些过量的ROS被认为会导致单纯性脂肪变性进展为NASH。另一方面,氧化应激会加剧肝细胞中的胰岛素敏感性,而肝脂肪变性会导致氧化应激。因此,氧化应激和胰岛素抵抗在NASH中可能相互作用。实际上,我们发现NASH患者的脂肪变性程度与血清硫氧还蛋白水平(氧化应激的一个标志物)相关。因此,我们提出氧化应激、胰岛素抵抗和脂肪变性的反馈环在NASH的发展中起重要作用。