陈欢　刘燕玲　刘学睿

[摘要目的 探讨大鼠早期酒精性肝损伤模型的建立方法，为研究早期酒精性肝损伤的发病分子机制提供理想动物模型。方法 24只雄性SD大鼠随机分为模型组（16只）和对照组（8只）。对照组饮用自来水；模型组饮用7%～56%梯度递增的白酒12周。取材前24 h和12 h，分别以56%白酒急性灌胃后处死大鼠。每天记录大鼠食用饲料量及饮用量；每周称量大鼠体重。采用全自动生化分析仪测定大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）含量。观察大鼠肝脏病理学和形态学改变。结果 12周后，模型组大鼠体重增长率为（61.67±1.98）% ，明显低于对照组的（160.09±3.12）% （P<0.05），肝脏指数模型组（3.74±0.54）高于对照组（2.85±1.26）（P <0.05）。模型组大鼠ALT、AST、TG、TC均较对照组增高（P<0.05），病理学检查模型组肝组织明显脂肪变性，伴局部炎症、坏死。结论 该模型操作简便，动物死亡率低，稳定，发病过程与临床类似，是研究早期酒精性肝损伤发病分子机制的理想模型。

[关键词]酒精性肝病；大鼠；肝病模型；肝功能

[中图分类号] R575 [文献标识码] A [文章编号] 1674-4721（2017）07（b）-0007-04

[Abstract]Objective To explore the method of establishing a model of early alcoholic liver disease（ALD） in rats in order to provide an ideal animal model for studying the molecular mechanism of early alcoholic liver injury.Methods Twenty-four male SD rats were randomly divided into experimental group （16 rats） and control group （8 rats）.In the control group，SD rats were fed with tap water.In the experimental group，SD rats were fed with alcohol of which the concentration of 7%-56% increased gradually for 12 weeks.During the experiment，the quantity of the fodder and the value of drinking were recorded everyday.Then the weight was weighed every week.24 and 12 hours before rats in experimental group were killed，they were treated with acute lavages with 56% alcohol.The activities of alanine aminotransferase （ALT），spartate aminotransferase （AST），riglyceride （TG） and total cholesterol （TC） in serum were determined by the fully automatic biochemical analyser.Moreover，the histological and morphological changes of liver tissues were observed. Results The growth rate of body mass was （160.09±3.12）% in the control group at the end of 12th week，while it was（61.67±1.98）% in the experimental group （P<0.05）.The ratio of liver body weight of the experimental group （3.74±0.54） was obviously increased compared with the control group （2.85±1.26）（P<0.05）.Compared with the control group，the levels of AST，ALT，TG and TC of the model group were clearly increased （P<0.05）.Meanwhile，the typical fatty liver pathologic changes，local inflammation and necrosis were observed in experimental group. Conclusion The results show that the ALD model with low mortality is stable and easy to copy，which is highly similar to the early ALD in human，and can be used in the study of ALD.

[Key words]Alcoholic liver disease；Rat；Liver disease model；Hepatic function

酒精濫用与依赖日益严重已成为世界性公共卫生问题。长期大量饮酒易导致酒精性肝病（alcoholic liver disease，ALD），早期表现为脂肪肝，可发展为酒精性肝炎、肝纤维化及肝硬化；严重酗酒可造成广泛肝细胞坏死甚至肝衰竭[1-3]。选择与人类ALD相似的动物模型对研究其发病机制具有重要意义。本实验建立酒精浓度梯度递增的白酒长期喂养基础上高浓度酒精急性灌胃诱导的大鼠肝损伤模型，旨在为ALD建立有价值的研究工具。

1材料与方法

1.1材料

SD雄性大鼠（清洁级）24只[西南医科大学动物实验中心提供，SCXK（川）2013-17]，平均体重（200±15）g，饲养条件：温度20～25℃，相对湿度40%～70%。

1.2主要试剂

56度的北京红星二锅头白酒；HE染色剂：珠海贝索技术有限公司；丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）试剂盒：南京建成生物有限公司。……