Fan Jian-gao, Ding Xiao-dong, Wang Guo-liang, Xu Zheng-jie, Tian Li-yan, Zheng Xiao-ying
Department of Gastroenterology, Shanghai First People's Hospital, Jiaotong University, Shanghai 200080, China.
Zhonghua Gan Zang Bing Za Zhi. 2005 May;13(5):374-7.
To investigate the expression of uncoupling protein 2 (UCP2) and its relationship to the content of adenosine triphosphate (ATP) in livers of nonalcoholic fatty liver disease (NAFLD) rats fed a fat-rich diet.
To produce a NAFLD model, a fat-rich diet, consisting of 10% lard oil + 2% cholesterol, was given to Sprague-Dawley rats for a period of 8, 12, 16 and 24 weeks. The normal control rats were fed normal diets. The expressions of UCP2 in the liver were detected by immunohistochemistry and semi-quantitative RT-PCR. The content of ATP of liver was measured by fluorometry.
Simple fatty livers were observed in the model group after 8 weeks. From 12 week to 24 week, the livers of the model group rats gradually progressed from simple steatohepatitis to steatohepatitis with pericellular fibrosis. Both immunohistochemistry and semi-quantitive RT-PCR suggested the up-regulated expression of UCP2 in these NAFLD rat livers. The hepatic expression of UCP2 mRNA in the model group was increased with time, and peaked in 24 week by 4.2 times compared to the control group ( t = 16.474, P < 0.01). The ATP content of livers was significantly reduced in the model group compared with the control group at 16 weeks [(2.97+/-0.48) x 10(-8) micromol/g vs. (2.25+/-0.55) x 10(-8) micromol/g, t = 2.419, P < 0.05] and 24 weeks [(2.97+/-0.48) x 10(-8) micromol/g vs. (1.99+/-0.66) x 10(-8) micromol/g, t = 3.248, P < 0.01]. Furthermore, there was a negative correlation between the UCP2 mRNA expression and the content of ATP in the livers of the NAFLD group (r = -0.93, P < 0.01).
The rat model of NAFLD could be replicated sucessfully by feeding a fat-rich diet for 24 weeks, and the mRNA and its protein of UCP2 were expressed un-regulated in livers of NAFLD. The increasing UCP2 might play a role in the reduction of ATP content in livers of the NAFLD rats.
研究高脂饮食喂养的非酒精性脂肪性肝病（NAFLD）大鼠肝脏中解偶联蛋白2（UCP2）的表达及其与三磷酸腺苷（ATP）含量的关系。
为建立NAFLD模型，将由10%猪油+2%胆固醇组成的高脂饮食喂给Sprague-Dawley大鼠8、12、16和24周。正常对照大鼠喂以正常饮食。采用免疫组织化学和半定量逆转录-聚合酶链反应（RT-PCR）检测肝脏中UCP2的表达。用荧光法测定肝脏ATP含量。
8周后模型组出现单纯性脂肪肝。从12周到24周，模型组大鼠肝脏逐渐从单纯性脂肪性肝炎发展为伴有细胞周围纤维化的脂肪性肝炎。免疫组织化学和半定量RT-PCR均提示这些NAFLD大鼠肝脏中UCP2表达上调。模型组肝脏UCP2 mRNA表达随时间增加，24周时达到峰值，与对照组相比增加了4.2倍（t = 16.474，P < 0.01）。与对照组相比，模型组在16周时肝脏ATP含量显著降低[（2.97±0.48）×10⁻⁸ μmol/g对（2.25±0.55）×10⁻⁸ μmol/g，t = 2.419，P < 0.05]，24周时也显著降低[（2.97±0.48）×10⁻⁸ μmol/g对（1.99±0.66）×10⁻⁸ μmol/g，t = 3.248，P < 0.01]。此外，NAFLD组肝脏中UCP2 mRNA表达与ATP含量呈负相关（r = -0.93，P < 0.01）。
高脂饮食喂养24周可成功复制NAFLD大鼠模型，NAFLD大鼠肝脏中UCP2的mRNA及其蛋白表达上调。UCP2增加可能在NAFLD大鼠肝脏ATP含量降低中起作用。
