关键词: 非酒精性脂肪性肝病, 高脂饮食, 内生性乙醇, 乙醇脱氢酶, 乙醛脱氢酶, 大鼠

Abstract: Objective To observe the effect of high-fat diet and high-fructose diet on hepatic histology, endogenous ethanol and related ethanol metabolic enzymes including alcohol dehydrogenase 1（ADH1） and aldehyde dehydrogenase 2 （ALDH2） in rats. Methods Eighteen male Sprague Dawley rats were randomly divided into control group（n=6）,high-fat diet group （n=6） and high-fructose diet group（n=6）. At the end of 16th week,nonalcoholic fatty liver disease（NAFLD） activity score（NAS） of liver tissues was evaluated. The endogenous ethanol in portal venous blood were detected. The mRNA levels of hepatic ADH1 and ALDH2 were detected by real time PCR. The protein levels of hepatic ADH1 and ALDH2 were detected by Western blot. The activity of ADH1 was detected by ADH1 enzyme activity kits. Results At the end of 16th week, the liver tissues of rats in high-fructose group were simple steatosis and of rats in high-fat group presented severe hepatic inflammation. The NAS score in high-fat group was 5.40±0.32,significantly higher than in normal group 【（1.10±0.25）,P<0.05】 or in high-fructose group 【（2.94±0.40）,P<0.05】;Serum endogenous ethanol levels in high-fat group 【（1.30±0.15）nmol/μL】 was significantly higher than that in normal group 【（1.00±0.10）nmol/μL,P<0.05）】 or in high-fructose group【（1.04±0.23）nmol/μL,P<0.05）】;the mRNA levels of ADH1 in high-fat group was significantly 1.30 fold or 1.36 fold higher than that in high-fructose group and in normal group respectively（P<0.05）; the mRNA level of ALDH2 in high-fat group was significantly 1.55 fold or 1.44 fold higher than that in high-fructose group and in normal group respectively（P<0.05）;the protein expression levels of ADH1 in high-fat group was significantly 2.56 fold or 2.52 fold higher than that in high-fructose group and in normal group respectively（P<0.05）,and the ALDH2 protein in high-fat group was significant 1.41 fold or 1.57 fold higher than that in high-fructose group and in normal group respectively（P<0.05）;meanwhile, the activity of ADH enzyme in high fat group（175±28）μ/L was significant higher when compared with that in normal group 【（72±13）μ/L,P<0.05）】 and in high-frutose group 【（78±9）μ/L,P<0.05）】. Conclusion High-fat diet can significantly increase the endogenous ethanol levels in the portal vein, and up-regulate the protein expression of ADH enzyme in the livers.

Key words: Nonalcoholic fatty liver disease, High-fat diet, Endogenous ethanol, Alcohol dehydrogenase 1, Aldehyde dehydrogenase 2, Rats