两种Lieber-DeCarli液体饲料诱导的小鼠酒精性肝损伤模型的建立  

Establishment of two kinds of Lieber-DeCarli liquid diet-induced alcoholic liver diseases in mice

作　　者：曾涛[1] 姜璐璐[1] 张翠丽[1] 赵秀兰[1] 于丽华[1] 朱振平[1] 谢克勤[1] 

机构地区：[1]山东大学公共卫生学院毒理学研究所,山东济南250012

出　　处：《毒理学杂志》2012年第4期258-262,共5页Journal of Toxicology

基　　金：国家自然科学基金(81102153);山东省自然科学基金(ZR2011HQ026);山东大学自主创新基金(2010GN045)

摘　　要：目的建立常规和低脂Lieber-DeCarli液体饲料诱导的酒精性肝损伤小鼠模型。方法健康雄性昆明小鼠50只,随机分为5组(n=10),即颗粒饲料组、常规对照组、常规乙醇组、低脂对照组和低脂乙醇组。各组小鼠分别喂饲相应的饲料4周,记录每日液体饲料消耗量。4周末处死小鼠,测定血清转氨酶的活性、血清和肝脏甘油三酯(TG)的含量。制备肝脏冰冻切片,苏丹Ⅲ染色观察肝细胞脂肪变性。结果造模过程中,常规和低脂乙醇组小鼠乙醇摄入量分别为24～34 g/kg.bw/d和15～25 g/kg.bw/d。造模结束时,两液体饲料对照组小鼠体重略高于颗粒饲料组小鼠体重;两乙醇组小鼠肝脏系数均显著高于各自对照组小鼠的肝脏系数(P<0.01)。生化结果显示,常规乙醇组小鼠血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性以及血清和肝脏TG含量均显著高于常规对照组水平(P<0.01);低脂乙醇组小鼠血清ALT的活性和肝脏TG含量均显著高于低脂对照组水平(P<0.05)。病理检查结果显示,乙醇组小鼠肝脏切片中有大量脂滴蓄积。结论自行配制常规和低脂液体饲料,喂饲小鼠4周,均可诱导小鼠出现酒精性肝损伤。该模型简单方便,可用于酒精性肝损伤分子机制研究和防治药物的筛选。Objective To establish regular and low-fat Liebier-DeCarli liquid diet-induced liver diseases in mice. Method Male Kun-Ming mice were randomized into 5 groups （ n = 10）, i.e. normal diet group, regular control group, regular ethanol group,low-fat control group, and low-fat ethanol group. Two kinds of Lieber-DeCarli liquid diet were prepared, and administered to mice for consecutive 4 weeks. The volume of liquid diet consumed each day was recorded to calculate the energy intake and ethanol intake. The serum and hepatic biochemical indices were examined by using commercial assay kits. Hepatic frozen sections were stained with Sudan Ill staining. Results The ethanol intake was about 24-34 g/kg·bw/d and 15-25 g/kg·bw/d for regular and low-fat ethanol groups, respectively. The final body weight of the two liquid control groups mice was a little higher than that of normal diet group, while the liver indexes of mice in two ethanol groups were obviously larger than those of respective liquid control groups （P 〈 0. 01 ）. Besides, the activities of the serum ALT and AST, and the contents of serum and hepatic TG in the regular ethanol groups were significantly higher than those of Regular control groups （ P 〈0. 01 ）, while the ALT activity and hepatic TG level were significantly higher than those of low-fat control group （P 〈 0.05 ）. Furthermore, many lipid droplets were found to be accumulated in the hepatic section of two ethanol groups＇ mice. Conclusion Lieber-DeCarli liquid diets could induce liver injury in mice, which could be used for the mechanisms exploration and the evaluation of the hepato-protective drugs.

关 键 词：乙醇 Lieber-DeCarli液体饲料 酒精性脂肪肝 甘油三酯 

分 类 号：R994.4[医药卫生—毒理学]