Objective: To establish overfed zebrafish model for non-alcoholic steatohepatitis. Methods: The wild-type zebrafish was fed 3 times a day with normal diet. Body length, weight, and triglyceride levels were measured after 20 days of feeding. The changes in expression of genes associated with cholesterol metabolism, lipid metabolism, endoplasmic reticulum stress, and inflammation were detected by quantitative PCR. Liver tissue sections were stained with H&E. Statistical analyses between groups were compared using t-test. Results: The body length (0.71±0.014) cm and body weight (44.83±1.833) mg of model group were higher than that of control group (0.50±0.009) cm and body weight (19.33±2.753) mg (total (body length) = 12.36, total (body weight) = 7.71, P < 0.01). Triglyceride content in the model group was (59.15 ± 0.5612) μmol / L, higher than the control group (16.71 ± 0.3562) μmol / L (t = 63.84, P < 0.001). Quantitative PCR results showed that the expression of genes related to cholesterol synthesis in the model group was higher than that in the control group (P < 0.01). The expression levels of lipid production and lipid oxidation related factors in the model group were higher than the control group. The difference between the two groups was statistically significant (P < 0.05). The expression of inflammation-related factors in the model group was higher than that in the control group (P < 0.001), and the expression of genes related to endoplasmic reticulum stress in the model group was higher than that to control group (P<0.001). Liver H&E staining showed that the model group had pathological changes such as large bulla and vesicles compared to the control group. Conclusion: A continuous 3 times 20 days of normal diet can simulate the disease characteristics of human non-alcoholic steatohepatitis in a zebrafish.
目的： 通过给予过量饮食的方法建立斑马鱼非酒精性脂肪性肝炎模型。 方法： 采用每日给予3倍于正常饮食的方式喂养野生型斑马鱼，20 d后检测其体长、体质量、体内甘油三酯等指标。用定量PCR检测与胆固醇代谢、脂质代谢、内质网应激及炎症等相关基因的表达变化。用肝脏组织切片HE染色评价病理学变化。组间比较采用t检验进行统计学分析。 结果： 模型组斑马鱼体长（0.71±0.01）cm和体质量（44.83±1.83）mg高于对照组的体长（0.50±0.01）cm和体质量（19.33±2.75）mg（t(体长)= 12.36，t(体质量)= 7.71，P<0.01），模型组体内三酰甘油的含量为（59.15±0.56）μmol/L，高于对照组的（16.71±0.36）μmol/L（t = 63.84，P<0.01）。定量PCR结果显示模型组与胆固醇合成相关基因表达高于对照组（P<0.01）、模型组与脂质生成和脂质氧化相关因子表达量较对照组升高，两组比较，差异有统计学意义（P<0.05）、模型组与炎症相关的因子表达量也高于对照组（P<0.01）、模型组与内质网应激相关基因表达高于对照组（P<0.01）。肝脏HE染色结果显示模型组相较于对照组出现脂肪大泡和小泡等病理学改变。 结论： 连续给予3倍于正常量的饮食20 d，可在斑马鱼体内模拟人类非酒精性脂肪性肝炎的疾病特征。.
Keywords: Fatty liver, non-alcoholic; Food, formulated; Non-alcoholic steatohepatitis; Zebrafish.