非酒精性脂肪性肝纤维化小鼠模型的建立及炎症因子的表达  

Establishment of Nonalcoholic Fatty Liver Fibrosis Model and Expression of Inflammatory Factors in Mice

作　　者：杨华[1] 赵亚娟[2] 欧强[2] 

机构地区：[1]上海市公共卫生临床中心,上海201508 [2]上海市第八人民医院,上海200235

出　　处：《实验动物与比较医学》2017年第1期20-24,共5页Laboratory Animal and Comparative Medicine

基　　金：上海市第八人民医院人才引进科研基金(BY201406)

摘　　要：目的建立非酒精性脂肪性肝纤维化小鼠模型,观察其病变及炎症因子的表达情况。方法20只雄性C57BL/6J小鼠随机分成对照组、非酒精性脂肪性肝纤维化模型组。对照组小鼠予以蛋氨酸-胆碱充足(MCS)饲料喂养,模型组小鼠予以蛋氨酸-胆碱缺乏(MCD)饲料喂养造模。于造模8周末处死小鼠。观察肝脏组织病理学变化,检测小鼠血清草氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆固醇(TC)、甘油三酯(TG)肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平。结果造模8周末,模型组小鼠体质量显著下降。肝组织病理学观察显示严重肝脂肪变,肝细胞水肿,可见点灶状坏死及淋巴细胞浸润,局灶见界面肝炎,汇管区扩大,纤维组织增生。模型组小鼠肝脏炎症活动度得分和纤维化得分均显著高于对照组(P<0.01)。模型组小鼠血清ALT、AST、TNF-α、IL-6与对照组比较显著升高,而TG和TC水平显著下降(P<0.01)。结论小鼠经MCD饲料喂养8周出现严重肝脂肪变、肝纤维化和炎症因子高表达,表明成功诱导小鼠非酒精性脂肪性肝纤维化模型。该方法造模简单,成模快,存活率高,适合用于非酒精性脂肪性肝纤维化发病机制和药物干预等方面的研究。Objective To establish the non-alcoholic fatty liver fibrosis model in mice and observe the pathological changes and the expression of inflammatory factors. Methods Twenty male C57BL/6J mice were randomly divided into control group and model group. The mice in control group were fed with methionine and choline-supplement（MCS） diet, and the model group were fed with methionine choline deficiency （MCD） diet. The mice were weighed and sacrificed at after 8 weeks feeding. The histopathological changes in liver were observed. The level of serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, cholesterol （TC）, triglyceride （TG）, tumor necrosis factor -α （TNF-α） and interleukin （IL-6） were detected. Results The body weight of mice in the model group decreased significantly at the end of the study. Severe hepatic steatosis, liver cell edema, visible focal necrosis and focal lymphocytic infiltration, interface hepatitis, periportal enlargement, hyperplasia of fibrous tissue were observed.The scores of liver inflammation activity and fibrosis score in model group were significantly higher than those in control group （P〈0.01）.The level of serum ALT, AST, TNF-α, IL-6 were significantly higher in the model group than that of control group （P〈0.01）. Conclusion After feeding mice with MCD diet feeding for 8 weeks, non-alcoholic fatty liver fibrosis model of mice was successfully induced. The modeling method was simple, rapid, and with has high survival rate. It is suitable for the pathogenesis and drug intervention study of nonalcoholic fatty liver fibrosis.

关 键 词：非酒精性脂肪性肝纤维化 蛋氨酸-胆碱缺乏(MCD) C57BL/6J小鼠 炎症因子 

分 类 号：R-332[医药卫生] R575.2