Liu Wensheng, Baker Susan S, Baker Robert D, Zhu Lixin
Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, 3435 Main Street, 422BRB, Buffalo, NY 14214, USA.
Curr Drug Targets. 2015;16(12):1301-14. doi: 10.2174/1389450116666150427155342.
Nonalcoholic fatty liver disease (NAFLD) represents a broad spectrum of histological abnormalities with clinical presentations ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH). Some NAFLD patients may progress to cirrhosis and ultimately hepatocellular carcinoma (HCC). Hepatic steatosis, the hallmark of NAFLD, is defined by the accumulation of triglycerides (TGs) in more than 5% of the hepatocytes. NASH is characterized by inflammation along with variable degrees of fibrosis in addition to steatosis. NAFLD has been considered to be the hepatic manifestation of metabolic syndrome (MS), as it is frequently associated with MS conditions such as insulin resistance (IR) and obesity. Hepatic steatosis mainly results from disrupted homeostasis of lipid metabolism in the setting of IR. Although the mechanism underlying the progression from steatosis to NASH is still not fully elucidated, mounting evidence has suggested oxidative stress (OS) to be a key driving force. Elevated OS has been well documented in NAFLD patients. OS can cause direct damages to lipid, protein, and DNA molecules and trigger the inflammatory and fibrogenesis signaling pathways, which promotes the progression from steatosis to NASH. OS may also have various effects on antioxidant defense mechanisms. Overproduced reactive oxygen species (ROS) may directly deplete antioxidant molecules such as glutathione (GSH) and inhibit the activities of antioxidant enzymes such as superoxide dismutase (SOD). ROS may also induce the expression of antioxidant genes to counteract the OS effects. The aim of this review is to discuss oxidative stress and antioxidant mechanisms in NAFLD.
非酒精性脂肪性肝病（NAFLD）表现为一系列广泛的组织学异常，临床表现从肝脂肪变性到非酒精性脂肪性肝炎（NASH）不等。一些NAFLD患者可能进展为肝硬化，最终发展为肝细胞癌（HCC）。肝脂肪变性是NAFLD的标志，定义为超过5%的肝细胞内甘油三酯（TGs）积聚。NASH的特征是除脂肪变性外还伴有不同程度的炎症和纤维化。NAFLD被认为是代谢综合征（MS）的肝脏表现，因为它经常与MS相关疾病如胰岛素抵抗（IR）和肥胖症有关。肝脂肪变性主要是在IR情况下脂质代谢稳态破坏的结果。尽管从脂肪变性进展到NASH的潜在机制仍未完全阐明，但越来越多的证据表明氧化应激（OS）是关键驱动力。NAFLD患者中OS升高已有充分记录。OS可对脂质、蛋白质和DNA分子造成直接损害，并触发炎症和纤维化信号通路，从而促进从脂肪变性到NASH的进展。OS也可能对抗氧化防御机制产生各种影响。过量产生的活性氧（ROS）可能直接消耗抗氧化分子如谷胱甘肽（GSH），并抑制抗氧化酶如超氧化物歧化酶（SOD）的活性。ROS还可能诱导抗氧化基因的表达以抵消OS的影响。本综述的目的是讨论NAFLD中的氧化应激和抗氧化机制。
