Irie M, Sohda T, Iwata K, Kunimoto H, Fukunaga A, Kuno S, Yotsumoto K, Sakurai K, Iwashita H, Hirano G, Ueda S I, Yokoyama K, Morihara D, Nishizawa S, Anan A, Takeyama Y, Sakamoto M, Shakado S, Sakisaka S
Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
J Int Med Res. 2012;40(3):924-33. doi: 10.1177/147323001204000311.
This study investigated oxidative stress in the liver, by determining hepatic expression and serum levels of γ-glutamyltranspeptidase (GGT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in different stages of nonalcoholic fatty liver disease (NAFLD), and assessed whether GGT can differentiate between the various stages of NAFLD.
Expression of GGT and 8-OHdG was examined in biopsy specimens by immunohistochemistry, and serum GGT and 8-OHdG levels were measured by enzyme-linked immuno sorbent assays in patients with simple fatty liver (n = 10), nonalcoholic steatohepatitis (NASH; n = 10) and, as a control, in alcoholic liver disease (ALD; n = 10).
Hepatic tissue expression of GGT and 8-OHdG was seen in ALD, NASH and fatty liver patients. The percentage of hepatocytes positive for 8-OHdG expression and serum 8-OHdG levels was significantly higher in patients with NASH than simple fatty liver. Serum GGT levels were increased in all cases with ALD, NASH and fatty liver, and correlated significantly with serum levels of 8-OHdG in ALD and NASH, but not in simple fatty liver.
Levels of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8-OHdG and the development of NASH.
本研究通过测定非酒精性脂肪性肝病（NAFLD）不同阶段肝脏中γ-谷氨酰转肽酶（GGT）的表达及血清水平和8-羟基-2'-脱氧鸟苷（8-OHdG），来研究肝脏中的氧化应激，并评估GGT是否能够区分NAFLD的各个阶段。
通过免疫组织化学检测活检标本中GGT和8-OHdG的表达，采用酶联免疫吸附测定法测量单纯性脂肪肝患者（n = 10）、非酒精性脂肪性肝炎（NASH；n = 10）患者以及作为对照的酒精性肝病（ALD；n = 10）患者血清中的GGT和8-OHdG水平。
在ALD、NASH和脂肪肝患者中均可见肝脏组织GGT和8-OHdG的表达。NASH患者中8-OHdG表达阳性的肝细胞百分比及血清8-OHdG水平显著高于单纯性脂肪肝患者。ALD、NASH和脂肪肝患者的血清GGT水平均升高，且在ALD和NASH中血清GGT水平与8-OHdG血清水平显著相关，而在单纯性脂肪肝中无此相关性。
脂肪肝患者的GGT水平可能通过抑制8-OHdG水平并防止进展为NASH来代偿轻度氧化应激；然而，进一步的氧化应激会导致8-OHdG水平升高及NASH的发生。
