Effect of high-fat diet on establishment of a rat non-alcoholic steatohepatitis/liver fibrosis model
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摘要: 目的建立并研究高脂肪饮食导致大鼠非酒精性脂肪性肝炎(NASH)肝纤维化的动物模型。方法雄性SD大鼠60只,随机分成正常对照组30只和模型组30只,分别给予普通饲料与高脂饲料,于第4、8、12周末将正常对照组与模型组随机处死10只。分别检测血清学指标,取肝组织做HE染色及Masson染色,应用图像分析法对Masson染色进行纤维化面积定量分析。结果两组大鼠体重均增加,8周时肝指数明显升高,血清胆固醇及总甘油三酯8周开始与正常对照组比较差异具有统计学意义。转氨酶不同时间点均有升高,8、12周时与正常对照组比较差异具有统计学意义。高脂饮食4周末,HE染色可见肝小叶结构完整,汇管区见少量炎症细胞浸润,无病理性纤维化发生。8周末,达到脂肪肝的诊断标准,开始出现肝纤维化趋势。造模12周,大鼠肝组织脂肪变程度达重度,纤维化面积增大。结论经改良配方后,成功建立了大鼠NASH肝纤维化模型。Abstract: Objective This study was aimed to establish the rat model of nonalcoholic steatohepatitis/hepatic fibrosis induced by high-fat diet.Methods Sixty male Sprague-Dawley rats(N=60) were divided into control group(n=30) and model group(n=30) randomly.The rats of control group were fed with common forage and those of the model group were given high-fat diet.Ten rats in each group were terminated at 4,8 and 12 week respectively.The serum-markers were detected.The degrees of hepatic steatosis,inflammation and fibrosis were observed by HE staining and Masson staining.Masson staining was analyzed by image analysis system to achieve the fibrosis area quantitative analysis.Results The weight of Rats in both of these two groups increased.Compared to the control group,the liver index(liver weight/ body weight %),serum cholesterol,triglyceride and aminotransferase levels in the model group increased significantly after 8 weeks after which,the rats in model group were diagnosed with fatty liver disease.After 12 weeks high-fat diet,the pathological injury of the rats hepatic tissue became more and more severe,and resulted into liver fibrosis.Conclusion The rat model of nonalcoholic steatohepatitis/hepatic fibrosis has been established successfully by high-fat diet.
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Key words:
- liver cirrhosis /
- experimental /
- disease models
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[1]Varela-Rey M,Embade N,Ariz U,et al.Non-alcoholic steatohepatitis and animal models:Understanding the human disease[J].Biochem Cell Biol,2009,41(15):969-976. [2]Mori S,Yamasaki T,Sakaida I,et al.Hepatocellular carcinoma with nonalcoholic steatohepatitis[J].Gastroenterol,2004,39(4):391-396. [3]Zou Y,Li J,Lu C,et al.High-fat emulsion-induced rat of model of nonalcoholic steatohepatitis[J].Life Sci,2006,79(11):1100-1107. [4]Leclercq IA.Pathogenesis of steatohepatitis:insights from the study of animal models[J].Acta Gastroenterol Belg,2007,70(1):25-31. [5]Deng QG,She H,Cheng JH,et al.Steatohepatitis induced by intragastric overfeeding in mice[J].Hepatology,2005,42(4):905-914. [6]Elizabeth MB,Dina G,Tiniakos.Pathology of steatohepatitis[J].Best Practice Res clini Gastroenterol,2002,16(5):691-707. [7]王泰龄,刘霞,周元平,等.慢性肝炎炎症活动度及纤维化程度计分方案[J].中华肝病杂志,1998,6(4):195-197. [8]闫超,吴君,刘芙蓉,等.水砷暴露大鼠肝损伤和肝纤维化模型的建立[J].世界华人消化杂志,2009,17(9):862-866. [9]王倩,管小琴.大鼠非酒精性脂肪肝造模方法的改进[J].世界华人消化杂志,2007,15(11):1219-1244. [10]Miele L,Forgione A,Gasbarrini G,et al.Noninvasive assessment of fibrosis in non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)[J].Transl Res,2007,149(3):114-125. [11]Castera L.Non-invasive diagnosis of steatosis and fibrosis[J].Diabetes Metab,2008,36(6pt2):674-679. [12]刘俊平,范竹萍.从新视角评价非酒精性脂肪性肝炎动物模型[J].胃肠病学,2008,13(8):502-504. [13]范建高,钟岚,王国良,等.枯否氏细胞在大鼠非酒精性脂肪性肝炎发病中的作用[J].中华肝脏病杂志,2001,9(1):16-18. [14]徐正婕,范建高,王国良,等.高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型[J].世界华人消化杂志,2002,22(4):392-396. [15]张智,闪增郁,向丽华,等.大鼠实验性高脂血症两种造模方法的比较[J].国中医基础医学杂志,2004,10(2):33-34. [16]秦红波,曹浩强,华志元,等.高脂饮食致大鼠非酒精性脂肪肝模型的建立[J].南京医科大学学报,2008,28(8):973-976. [17]范建高,曾民德.脂肪性肝病[M].北京:人民卫生出版社,2002:18-27. [18]Deepa PR,Varalakshmi P.Favourable modulation of the inflammatory changes in hypercholesterolemic atherogenesis by a low-molecular-weight heparin derivative[J].Int J Cardiol,2006,106(3):338-347. [19]林克荣,杨慧莹.非酒精性脂肪性肝患者血清肿瘤坏死因子-α、脂联素水平与胰岛素抵抗的相关性[J].世界华人消化杂志,2007,15(24):2613-2618. [20]王文平,王佑民,王丽萍.肥胖大鼠非酒精脂肪肝与血清脂联素和肿瘤坏死因子α的关系及比格列酮干预[J].中国药理学通报,2008,24(2):265-268. [21]Bertolani C,Marra F.The role of adipokines in liver fibrosis[J].Pathophysiology,2008,15(2):91-101.
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