Marcolin Eder, Forgiarini Luiz Felipe, Tieppo Juliana, Dias Alexandre Simões, Freitas Luiz Antonio Rodrigues de, Marroni Norma Possa
Universidade Federal do Rio Grande do Sul.
Arq Gastroenterol. 2011 Jan-Mar;48(1):72-9. doi: 10.1590/s0004-28032011000100015.
Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied.
This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder.
Thirty male C57BL6 mice divided in two groups (n = 15) were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%.
The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity.
The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers.
非酒精性脂肪性肝炎是一种发病率高、诊断困难且尚无有效治疗方法的疾病。因此，人们对使用实验模型诱导非酒精性脂肪性肝炎并研究其发展途径进行了研究。
本研究旨在基于巴西生产的蛋氨酸和胆碱缺乏饮食建立一种非酒精性脂肪性肝炎实验模型，以评估该疾病引起的肝脏改变。
使用30只雄性C57BL6小鼠，分为两组（n = 15）：实验组喂食巴西PragSoluções®公司生产的蛋氨酸和胆碱缺乏饮食，对照组喂食正常饮食，持续2周。然后通过放血处死动物，采集血液进行全身生化分析，随后进行剖腹手术并全肝切除，制备材料进行组织学分析。采用独立样本t检验进行统计分析，显著性水平为5%。
接受蛋氨酸和胆碱缺乏饮食的小鼠体重减轻，肝损伤酶显著升高，全身血糖、甘油三酯、总胆固醇、高密度脂蛋白和极低密度脂蛋白水平降低。喂食蛋氨酸和胆碱缺乏饮食的小鼠中100%被诊断为非酒精性脂肪性肝炎。所有非酒精性脂肪性肝炎动物均表现出一定程度的大泡性脂肪变性、气球样变和炎症过程。喂食对照饮食的动物均未出现组织学改变。所有非酒精性脂肪性肝炎动物的脂质过氧化和抗氧化酶谷胱甘肽活性均显著升高。
本研究中探索的低成本且易于获取的蛋氨酸和胆碱缺乏饮食在动物模型中诱导脂肪变性和脂肪性肝炎非常有效，这些改变与在人类肝脏中观察到的相似。
