探讨β-arrestin 1在小鼠非酒精性脂肪性肝病（NAFLD）至肝癌自然病程中的变化和作用。

健康雄性C57BL/6小鼠80只，按随机数字表法随机分为素食组和高脂饮食组，每组各40只，分别给予素食（脂肪含量占总热量13%）和高脂饮食（脂肪含量占总热量58%），两组9、24周末时分别各处死8只小鼠，48周末时处死剩余小鼠。观察两组小鼠的肝癌发生率。Western blot法检测小鼠肝组织β-arrestin 1蛋白表达，TaqMan实时荧光定量RT-PCR检测其β-arrestin 1的mRNA水平。两组小鼠肝癌发生率的比较采用Fisher确切概率法，β-arrestin 1蛋白及其mRNA水平比较采用t检验。高脂饮食组β-arrestin 1蛋白和mRNA水平与高脂饮食时间的关系分析采用Spearman相关分析。

高脂饮食组小鼠肝癌的发生率为18%（4/22），明显高于素食组的0（0/23） （P=0.034）。高脂饮食组小鼠9周时肝组织β-arrestin 1蛋白表达水平为2.4±0.5,明显高于素食组的1.5±0.4（t=2.779，P<0.05）。高脂饮食组小鼠9、24、48周肝组织β-arrestin 1的mRNA水平分别为4.1±0.8、7.8±2.1、12.5±1.2，明显高于同期素食组的2.6±0.7、3.6±0.6、6.9±1.2（t=4.029，5.522，9.487；P<0.05）。高脂饮食组小鼠48周时肝癌组织的β-arrestin 1蛋白和mRNA水平为4.6±0.5、22.0±3.2，明显高于同期肝组织的1.6±0.4、12.5±1.2（t=9.600，7.837；P<0.05）。高脂饮食组的β-arrestin 1蛋白和mRNA水平与高脂饮食时间呈正相关（r=0.949，0.922；P<0.05）。

小鼠高脂饮食易发生NAFLD，且发生肝癌的几率明显升高。β-arrestin 1在此过程中可能起促进作用。

To investigate the changes and role of β-arrestin 1 in the course of non-alcoholic fatty liver disease (NAFLD) progressing to hepatocellular carcinoma (HCC).

Eighty healthy male C57BL/6 mice were randomized into the vegetarian diet group and the high fat diet group according to the random number table with 40 mice in each group. Mice in the vegetarian diet group were fed with vegetarian diet (13% calories in fat) and mice in the high fat diet group were fed with high fat diet (58% calories in fat). Eight mice in each group were decapitated at the end of 9 and 24 weeks. The rest mice in each group were decapitated at the end of 48 weeks. The incidence of HCC of two groups was observed. The expression of protein β-arrestin 1 in the liver tissues of mice was detected by Western blot and the mRNA level was examined using TaqMan real time fluorescence quantitative RT-PCR. The incidence of HCC in two groups was compared using Fisher's exact test, and the protein β-arrestin 1 expression and mRNA level of two groups were compared using t test. Spearman correlation analysis was used to evaluate the relationship between protein β-arrestin 1 expression, mRNA level and the feeding duration of high fat diet in high fat diet group.

The incidence of HCC in the high fat diet group was 18% (4/22), which was significantly higher than 0 (0/23) in the vegetarian diet group (P=0.034). The expression level of protein β-arrestin 1 in liver tissues of mice in the high fat diet group was 2.4±0.5 in the 9^th week, which was significantly higher than 1.5±0.4 in the vegetarian diet group (t=2.779, P<0.05). The β-arrestin 1 mRNA level in liver tissues of mice in the high fat diet group in the 9^th, 24^th and 48^th week were 4.1±0.8, 7.8±2.1 and 12.5±1.2 respectively, which were all significantly higher than 2.6±0.7, 3.6±0.6 and 6.9±1.2 in the vegetarian diet group (t=4.029, 5.522, 9.487; P<0.05) . The protein β-arrestin 1 and mRNA level in HCC tissues of mice in the high fat diet group in the 48^th week were 4.6±0.5 and 22.0±3.2, which were significantly higher than 1.6±0.4 and 12.5±1.2 in liver tissues at the same period (t=9.600, 7.837; P<0.05). The protein β-arrestin 1 and mRNA level in high fat diet group were positively correlated with the duration of high fat diet (r=0.949, 0.922; P<0.05).

It is likely to develop NALFD for the mice fed with high fat diet, and the incidence of HCC is significantly increased. β-arrestin 1 may play a role of accelerating the course of NAFLD progressing to HCC.