Aleynik S I, Leo M A, Aleynik M K, Lieber C S
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, New York 10468, USA.
Alcohol Clin Exp Res. 1998 Feb;22(1):192-6.
F2-isoprostanes (F2-IP) and 4-hydroxynonenal (4-HNE), peroxidation products of polyunsaturated fatty acids (PUFA), are considered the most reliable indicators of endogenous lipid peroxidation in vivo. To determine to what extent these are also altered in patients with alcoholic liver disease, plasma free and esterified F2-IP as well as 4-HNE were measured by GC/MS in 49 fasting subjects who underwent diagnostic percutaneous needle biopsies of the liver. Compared to patients with mild steatosis and no fibrosis, free F2-IP and 4-HNE were strikingly increased in individuals with alcoholic hepatitis. There was also a significant but lesser rise of 4-HNE in patients with perivenular fibrosis. An increase of F2-IP was also found in subjects with transition to, or complete, alcoholic cirrhosis, with a comparable trend for 4-HNE. By contrast, in patients who were drinking heavily up to 48 hr before admission, F2-IP were not abnormal, but they increased later (p < 0.005). Contrasting with plasma free F2-IP, esterified F2-IP were not significantly changed with fibrosis. Thus, whereas circulating esterified F2-IP were unchanged in patients with alcoholic liver disease, there was an increase in free F2-IP as well as 4-HNE during recovery from intoxication. The increase was not a result of accompanying hepatitis C but a function of the stage of alcoholic liver injury, possibly reflecting enhanced lipid peroxidation as well as interference with biliary excretion and/or hepatic esterification.
F2-异前列腺素（F2-IP）和4-羟基壬烯醛（4-HNE）是多不饱和脂肪酸（PUFA）的过氧化产物，被认为是体内内源性脂质过氧化最可靠的指标。为了确定在酒精性肝病患者中这些指标的改变程度，我们采用气相色谱/质谱法（GC/MS）对49例接受经皮肝穿刺活检的空腹受试者的血浆游离和酯化F2-IP以及4-HNE进行了检测。与轻度脂肪变性且无纤维化的患者相比，酒精性肝炎患者的游离F2-IP和4-HNE显著升高。肝静脉周围纤维化患者的4-HNE也有显著但较小幅度的升高。在向酒精性肝硬化转变或完全肝硬化的患者中也发现F2-IP升高，4-HNE也有类似趋势。相比之下，在入院前48小时内大量饮酒的患者中，F2-IP并无异常，但随后会升高（p<0.005）。与血浆游离F2-IP不同，酯化F2-IP不会随纤维化而发生显著变化。因此，在酒精性肝病患者中，循环酯化F2-IP未发生改变，而在从醉酒状态恢复过程中，游离F2-IP和4-HNE均升高。这种升高并非丙型肝炎所致，而是酒精性肝损伤阶段的一种表现，可能反映了脂质过氧化增强以及对胆汁排泄和/或肝脏酯化的干扰。
