本试验旨在研究敲除核转录因子NF⁃E2相关因子（ Nrf2）对高脂饲粮诱导小鼠肝脏氧化应激的影响。选择雄性野生型（ WT）和Nrf2基因敲除（ KO） ICR小鼠各20只，分别随机分成2组，每组各10只。1组WT和1组KO小鼠饲喂普通饲粮，为对照组，另2组饲喂高脂饲粮，为高脂组。试验期8周。结果显示，1）与对照组相比，WT和KO高脂组小鼠血清总胆固醇（ TC）、低密度脂蛋白（ LDL）含量和谷丙转氨酶（ ALT）、谷草转氨酶（ AST）活性极显著升高（ P＜0．01），碱性磷酸酶（ALP）活性显著或极显著升高（P＜0．05或P＜0．01），总蛋白（TP）含量极显著降低（ P＜0．01），但甘油三酯（ TG）和高密度脂蛋白（ HDL）含量变化不显著（ P＞0．05）。2） WT高脂组小鼠肝脏表现出小泡性脂肪变性， KO高脂组小鼠肝脏表现出严重的大泡性脂肪变性和温和的小泡性脂肪变性。3）与对照组相比，WT和KO高脂组小鼠肝脏中谷胱甘肽（ GSH）含量和超氧化物歧化酶（ SOD）活性显著或极显著降低（ P＜0．05或P＜0．01），而过氧化物酶（ POD）活性和丙二醛（ MDA）含量显著或极显著升高（ P＜0．05或P＜0．01）。与WT小鼠相比，KO高脂组小鼠肝脏中MDA含量增加49％，但GSH含量及SOD、POD活性变化不显著（ P＞0．05）。与WT对照组小鼠相比，KO高脂组小鼠肝脏中SOD、POD活性和MDA含量显著或极显著升高（ P＜0．05或P＜0．01），而GSH含量极显著降低（ P＜0．01）。由此可见，高脂诱导Nrf2基因缺失小鼠发生较严重的脂肪变性，同时高脂饲粮诱导的非酒精性脂肪肝模型小鼠肝脏发生氧化应激。%This experiment was conducted to study the effect of nuclear factor erythroid 2⁃like 2 ( Nrf2) disrup⁃tion on the development of oxidative stress of the mouse liver induced by high fat diet. Twenty male wild⁃type ( WT) and twenty Nrf2 knockout ( KO) mice on ICR background were randomly divided into two groups with ten mice in each group, respectively. Mice in the control group were fed the normal diet ( ND) , and the others were fed the high fat diet (HFD). The experiment lasted for 8 weeks.The results showed as follows:1) com⁃pared with the control group mice, the total cholesterol ( TC) , low⁃density lipoprotein ( LDL) content and ala⁃nine aminot ransferase ( ALT) , aspartat eaminotransferase ( AST) activity of WT and KO mice in HFD group were significantly increased (P<0.01), the alkaline phosphatase (ALP) activity was significantly increased ( P<0.05 or P<0.01) , the total protein ( TP) content was significantly decreased ( P<0.01) , but the triglycer⁃ides ( TG) and high⁃density lipoprotein ( HDL) content did not significantly changed ( P>0.05) . 2) Under the light microscope showed that WT high fat mice liver showed microvesicular steatosis, KO high fat mice liver showed gentle microvesicular steatosis and severe macrovesicular steatosis. 3 ) Compared with the control group, the glutathione ( GSH) content and superoxide dismutase ( SOD) activity of WT and KO mice in HFD group were significantly decreased ( P<0.05 or P<0.01) , while peroxidase ( POD) activity and malondialde⁃hyde (MDA) content were increased significantly (P<0.05 or P<0.01). Compared with the WT mice, the MDA content of KO mice in HFD group was increased 49%, but the GSH content and SOD, POD activity did not significantly changed ( P>0.05) . Compared with the WT mice in control group, the SOD, POD activity and MDA content of KO mice in HFD group were increased significantly (P<0.05 or P<0.01), while the GSH content was significantly decreased ( P<0.01) . The results indicated that Nrf2 deficient mice develope se⁃vere steatosis induced by high fat diet, and also high fat diet induces oxidative stress of nonalcoholic fatty liver disease mice.
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