NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis
NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis
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DOI：
10.1016/j.jhep.2006.08.025
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发表时间：
2007-02-01
影响因子：
25.7
通讯作者：
Farrell, Geoffrey C.
中科院分区：
文献类型：
--
作者：
dela Pena, Aileen;Leclercq, Isabelle A.;Farrell, Geoffrey C.
背景/目的：肝脏氧化应激是脂肪性肝炎代谢形式的一个关键特征，但促氧化剂的来源尚不清楚。NADPH氧化酶复合物对于炎性细胞中ROS的产生是关键的;任何一种组分（例如，gp 91（Phox））使NADPH氧化酶失活。我们测试了活化的炎症细胞是否有助于脂肪性hepatitis.Methods氧化应激：gp 91（phox-/-）和野生型（wt）小鼠喂养蛋氨酸和胆碱缺乏（MCD）的饮食。血清ALT，肝甘油三酯，组织病理学，脂质过氧化反应，NF-κ B的活化，NF-κ B调节基因和巨噬细胞趋化因子的表达进行了measured.Results：MCD饮食喂养10天后，gp 91（phox-/-）和野生型小鼠表现出同等的肝细胞损伤。8周后，尽管MCP和MIP趋化因子的mRNA水平相似，但gp 91（phox-/-）小鼠肝脏中活化的巨噬细胞比对照组少，但纤维化相似。NF-κ B B激活和ICAM-1，TNF-α和考克斯-2 mRNA的表达增加是显而易见的，在这两种基因型，但在gp 91（phox-/-）小鼠，这些基因的表达仅限于hepatocyte.Conclusions：一个功能性NADPH氧化酶复合物并没有重要贡献氧化应激在这个模型中，因此不是强制性的诱导或持久的饮食性脂肪性肝炎。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Hepatic oxidative stress is a key feature of metabolic forms of steatohepatitis, but the sources of pro-oxidants are unclear. The NADPH oxidase complex is critical for ROS generation in inflammatory cells; loss of any one component (e.g., gp91(Phox)) renders NADPH oxidase inactive. We tested whether activated inflammatory cells contribute to oxidant stress in steatohepatitis.Methods: gp91(phox-/-) and wildtype (wt) mice were fed a methionine and choline-deficient (MCD) diet. Serum ALT, hepatic triglycerides, histopathology, lipid peroxidation, activation of NF-kappa B, expression of NF-kappa B-regulated genes and macrophage chemokines were measured.Results:After 10 days of MCD dietary feeding, gp91(phox-/-) and wt mice displayed equivalent hepatocellular injury. After 8 weeks, there were fewer activated macrophages in livers of gp91(phox-/-) mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar. NF-kappa B activation and increased expression of ICAM-1, TNF-alpha and COX-2 mRNA were evident in both genotypes, but in gp91(phox-/-) mice, expression of these genes was confined to hepatocytes.Conclusions: A functional NADPH oxidase complex does not contribute importantly to oxidative stress in this model and therefore is not obligatory for induction or perpetuation of dietary steatohepatitis. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.