Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Antioxid Redox Signal. 2011 Jun;14(11):2121-35. doi: 10.1089/ars.2010.3263. Epub 2011 Mar 16.
To test the hypothesis that the inducible nitric oxide synthase (iNOS) is involved in mediating the toll-like receptor 4-dependent effects on the liver in the onset of fructose-induced steatosis, wild-type and iNOS knockout (iNOS(-/-)) mice were either fed tap water or 30% fructose solution for 8 weeks. Chronic consumption of 30% fructose solution led to a significant increase in hepatic steatosis and inflammation as well as plasma alanine-aminotransferase levels in wild-type mice. This effect of fructose feeding was markedly attenuated in iNOS(-/-) mice. Hepatic lipidperoxidation, concentration of phospho-IκB, nuclear factor κB activity, and tumor necrosis factor-α mRNA level were significantly increased in fructose-fed wild-type mice, whereas in livers of fructose-fed iNOS(-/-) mice, lipidperoxidation, phospho-IκB, nuclear factor κB activity, and tumor necrosis factor-α expression were almost at the level of controls. However, portal endotoxin levels and hepatic myeloid differentiation factor 88 expression were significantly higher in both fructose-fed groups compared to controls. Taken together, these data suggest that (i) the formation of reactive oxygen species in liver is a key factor in the onset of fatty liver and (ii) iNOS is involved in mediating the endotoxin/toll-like receptor 4-dependent effects in the development of fructose-induced fatty liver.
为了验证诱导型一氧化氮合酶（iNOS）是否参与介导 Toll 样受体 4 依赖的果糖诱导脂肪性肝病中的肝作用，将野生型和 iNOS 敲除（iNOS(-/-)）小鼠分别用自来水或 30%果糖溶液喂养 8 周。慢性摄入 30%果糖溶液导致野生型小鼠肝脂肪变性和炎症以及血浆丙氨酸转氨酶水平显著增加。果糖喂养的这种作用在 iNOS(-/-)小鼠中明显减弱。果糖喂养的野生型小鼠肝脂质过氧化、磷酸化 IκB、核因子 κB 活性和肿瘤坏死因子-α mRNA 水平显著增加，而果糖喂养的 iNOS(-/-)小鼠的脂质过氧化、磷酸化 IκB、核因子 κB 活性和肿瘤坏死因子-α表达几乎与对照组水平相当。然而，门脉内毒素水平和肝髓样分化因子 88 表达在果糖喂养组均明显高于对照组。总之，这些数据表明：（i）肝脏中活性氧的形成是脂肪肝发病的关键因素；（ii）iNOS 参与介导内毒素/Toll 样受体 4 依赖的果糖诱导脂肪性肝病的发展。
